MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'The Biochemical Journal' source. Thu, 09 Feb 2012 13:38:44 +0100 http://www.medworm.com/index.php?rid=5655084&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280012%26dopt%3DAbstract Authors: Sun X, Jones WT, Rikkerink EH Abstract IDPs (intrinsically disordered proteins) are highly abundant in eukaryotic proteomes and important for cellular functions, especially in cell signalling and transcriptional regulation. An IDR (intrinsically disordered region) within an IDP often undergoes disorder-to-order transitions upon binding to various partners, allowing an IDP to recognize and bind different partners at various binding interfaces. Plant-specific GRAS proteins play critical and diverse roles in plant development and signalling, and act as integrators of signals from multiple plant growth regulatory and environmental inputs. Possessing an intrinsically disordered N-terminal domain, the GRAS proteins constitute the first functionally required unfoldome from the pl... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5655084 Fri, 03 Feb 2012 16:48:46 +0100 5655084 http://www.medworm.com/index.php?rid=5655083&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280013%26dopt%3DAbstract Authors: Schaefer A, Nethe M, Hordijk PL Abstract Post-translational modifications are used by cells to link additional information to proteins. Most modifications are subtle and concern small moieties such as a phosphate group or a lipid. In contrast, protein ubiquitylation entails the covalent attachment of a full-length protein such as ubiquitin. The protein ubiquitylation machinery is remarkably complex, comprising more than 15 Ubls (ubiquitin-like proteins) and several hundreds of ubiquitin-conjugating enzymes. Ubiquitin is best known for its role as a tag that induces protein destruction either by the proteasome or through targeting to lysosomes. However, addition of one or more Ubls also affects vesicular traffic, protein-protein interactions and signal transduction. It is b... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5655083 Fri, 03 Feb 2012 16:48:35 +0100 5655083 http://www.medworm.com/index.php?rid=5655082&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22292813%26dopt%3DAbstract Authors: Tan M, Yan W, Liu RJ, Wang M, Chen X, Zhou XL, Wang ED Abstract Aminoacyl-tRNA synthetases (aaRSs) establish the rules of the genetic code by catalyzing the formation of aminoacyl-tRNA. The quality control for aminoacylation reaction is achieved by editing activity, which is usually carried out by a discrete editing domain. For leucyl-tRNA synthetase (LeuRS), the connective peptide 1 (CP1) domain is the editing domain responsible for hydrolyzing mis-charged tRNA. The CP1 domain is universally present in LeuRSs except LeuRS from Mycoplasma mobile (MmLeuRS). The substitute of CP1 in MmLeuRS is a nonapeptide (MmLinker). We show here that the MmLinker, which is critical for aminoacylation activity of MmLeuRS, could confer remarkable tRNA charging activity to the inactive CP1-d... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5655082 Wed, 01 Feb 2012 05:00:00 +0100 5655082 http://www.medworm.com/index.php?rid=5655081&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22295911%26dopt%3DAbstract Authors: Gellerich FN, Gizatullina Z, Trumbeckaite S, Korzeniewski B, Gaynutdinov T, Seppet E, Vielhaber S, Heinze HJ, Striggow F Abstract The glutamate-dependent respiration of isolated brain mitochondria (BM) is regulated by cytosolic Ca2+ (Ca2+cyt) (S0.5 = 225 ± 22 nM) through its effects on aralar. We now also demonstrate that the a-glycerophosphate-dependent respiration is controlled by Ca2+cyt (S0.5 = 60 ± 10 nM). At higher Ca2+cyt (< 600 nM), BM accumulate Ca2+ which enhances the rate of action of intramitochondrial dehydrogenases. The highest Ca2+-induced increments of state 3 respiration decrease with substrate in the order glutamate < a-ketoglutarate < isocitrate < a-glycerophosphate < pyruvate. Whereas the oxidation of pyruvate is only slightly influence... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5655081 Wed, 01 Feb 2012 05:00:00 +0100 5655081 http://www.medworm.com/index.php?rid=5619089&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248338%26dopt%3DAbstract Authors: Roach PJ, Depaoli-Roach AA, Hurley TD, Tagliabracci VS Abstract Glycogen is a branched polymer of glucose that acts as a store of energy in times of nutritional sufficiency for utilization in times of need. Its metabolism has been the subject of extensive investigation and much is known about its regulation by hormones such as insulin, glucagon and adrenaline (epinephrine). There has been debate over the relative importance of allosteric compared with covalent control of the key biosynthetic enzyme, glycogen synthase, as well as the relative importance of glucose entry into cells compared with glycogen synthase regulation in determining glycogen accumulation. Significant new developments in eukaryotic glycogen metabolism over the last decade or so include: (i) three-dimens... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619089 Sun, 22 Jan 2012 20:55:46 +0100 5619089 http://www.medworm.com/index.php?rid=5619088&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248339%26dopt%3DAbstract Authors: Mullen TD, Hannun YA, Obeid LM Abstract Sphingolipid metabolism in metazoan cells consists of a complex interconnected web of numerous enzymes, metabolites and modes of regulation. At the centre of sphingolipid metabolism reside CerSs (ceramide synthases), a group of enzymes that catalyse the formation of ceramides from sphingoid base and acyl-CoA substrates. From a metabolic perspective, these enzymes occupy a unique niche in that they simultaneously regulate de novo sphingolipid synthesis and the recycling of free sphingosine produced from the degradation of pre-formed sphingolipids (salvage pathway). Six mammalian CerSs (CerS1-CerS6) have been identified. Unique characteristics have been described for each of these enzymes, but perhaps the most notable is the ability of... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619088 Sun, 22 Jan 2012 20:55:32 +0100 5619088 http://www.medworm.com/index.php?rid=5619082&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22260630%26dopt%3DAbstract Authors: Walters JN, Bickford JS, Newsom KJ, Beachy DE, Barilovits SJ, Herlihy JD, Nick HS Abstract The studies of prostaglandin E2 (PGE2) biosynthesis have primarily focused on the role of cyclooxygenases. Efforts have shifted towards the specific PGE2 terminal synthases, particularly microsomal PGE synthase (mPGES-1), which has emerged as the crucial inducible synthase with roles in pain, cancer and inflammation. mPGES-1 is induced by proinflammatory cytokines with studies focusing on the proximal promoter, mediated specifically through Egr-1. Numerous studies demonstrate that the mPGES-1 promoter alone cannot account for the level of IL-1β induction. We identified two DNase I hypersensitive sites within the proximal promoter near the Egr-1 element and a novel distal site near -... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619082 Fri, 20 Jan 2012 05:00:00 +0100 5619082 http://www.medworm.com/index.php?rid=5619085&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257123%26dopt%3DAbstract In this study, we investigated the involvement of γ-enolase in PI 3-K/Akt (phosphatidylinositol 3-kinase/Akt) and MAPK/ERK (mitogen-activated protein kinase/ extracellular-signal-regulated kinase) signaling, the two pathways triggered predominantly by neurotrophic factors. While the PI 3-K/Akt pathway, rather than the MAPK/ERK pathway, is involved in γ-enolase-enhanced cell survival, γ-enolase-stimulated neurite outgrowth requires both pathways, i.e. the activation of both PI 3-K and ERK1/2, leading to subsequent expression of growth cone-specific GAP-43 protein. MEK (mitogen-activated protein kinase kinase) and PI 3-K inhibition blocked or attenuated the neurite outgrowth associated with dynamic remodeling of the actin-based cytoskeleton. We show that γ-enolase-mediated PI 3-K activat... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619085 Thu, 19 Jan 2012 05:00:00 +0100 5619085 http://www.medworm.com/index.php?rid=5619084&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257159%26dopt%3DAbstract In this study, we show that EGCG-induced apoptotic activity is attributed to a lipid raft clustering mediated through 67-kDa laminin receptor (67LR) that is significantly elevated in multiple myeloma (MM) cells relative to normal peripheral blood mononuclear cells, and that acid sphingomyelinase (aSMase) is critical for the lipid raft clustering and the apoptotic cell death induced by EGCG. We also found that EGCG induces aSMase translocation to the plasma membrane and protein kinase C delta (PKCδ) phosphorylation at Ser664, which was necessary for aSMase/ceramide signaling, via 67LR. Additionally, orally administered EGCG activated PKCδ and aSMase in a murine MM xenograft model. These results elucidate a novel cell death pathway triggered by EGCG for the specific killing of MM cells. ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619084 Thu, 19 Jan 2012 05:00:00 +0100 5619084 http://www.medworm.com/index.php?rid=5619083&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257180%26dopt%3DAbstract Authors: Carrino DA, Mesiano S, Barker NM, Hurd WW, Caplan AI Abstract Fibrosis is the formation of excess and abnormal fibrous connective tissue as a result of either a reparative or reactive process. A defining feature of connective tissue is its extracellular matrix, which provides structural support and also influences cellular activity. Two common human conditions that result from fibrosis are uterine fibroids (leiomyomas) and keloid scars. Because these conditions share a number of similarities and because their growth is due primarily to excessive extracellular matrix deposition, we compared the proteoglycans of uterine fibroids and keloid scars to corresponding normal tissues. Our analysis indicates that uterine fibroids and keloid scars contain higher amounts of proteoglyc... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619083 Thu, 19 Jan 2012 05:00:00 +0100 5619083 http://www.medworm.com/index.php?rid=5619087&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250954%26dopt%3DAbstract Authors: Cruz-Garcia D, Diaz-Ruiz A, Rabanal-Ruiz Y, Peinado JR, Gracia-Navarro F, Castaño JP, Montero-Hadjadje M, Tonon MC, Vaudry H, Anouar Y, Vazquez-Martinez R, Malagon MM Abstract Golgi-associated long coiled-coil proteins, often referred to as golgins, are involved in the maintenance of the structural organization of the Golgi apparatus and the regulation of membrane traffic events occurring in this organelle. Little information is available on the contribution of golgins to Golgi function in cells specialized in secretion such as endocrine cells or neurons. Here, we characterize the intracellular distribution as well as the biochemical and functional properties of a novel long coiled-coil protein present in neuroendocrine tissues, neuroendocrine long coiled-coil protein 1 (... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619087 Wed, 18 Jan 2012 05:00:00 +0100 5619087 http://www.medworm.com/index.php?rid=5619086&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250985%26dopt%3DAbstract Authors: Hou TY, Monk JM, Fan YY, Barhoumi R, Chen YQ, Rivera GM, McMurray DN, Chapkin RS Abstract n-3 polyunsaturated fatty acids (PUFA), i.e. docosahexaenoic acid (DHA), found in fish oil, exhibit anti-inflammatory properties; however, the molecular mechanisms remain unclear. Since phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2) resides in raft domains and DHA can alter the size of rafts, we hypothesized that PI(4,5)P2 and downstream actin remodeling are perturbed by the incorporation of n-3 PUFA into membranes, resulting in suppressed T cell activation. CD4+ T cells isolated from Fat-1 transgenic mice (membranes enriched in n-3 PUFA) exhibited a 50% decrease in PI(4,5)P2. Upon activation by plate bound anti-CD3/anti-CD28 or PMA/ionomycin, Fat-1 CD4+ T cells failed to metabol... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619086 Wed, 18 Jan 2012 05:00:00 +0100 5619086 http://www.medworm.com/index.php?rid=5619093&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248097%26dopt%3DAbstract Authors: Selvakumar D, Drescher MJ, Dowdall JR, Khan KM, Hatfield JS, Ramakrishnan NA, Drescher DG Abstract The molecular characteristics of cyclic nucleotide-gated (CNG) channels in auditory/vestibular hair cells are largely unknown, unlike those of CNG channels mediating sensory transduction in vision and olfaction. Here, we report full-length sequence for three CNGA3 variants in a hair cell preparation from the trout saccule with high identity to CNGA3 in olfactory receptor neurons/cone photoreceptors. A custom antibody targeting amino terminus sequence immunolocalized CNGA3 to the stereocilia and subcuticular plate region of saccular hair cells. The cytoplasmic carboxyl terminus of CNGA3 was found by yeast two-hybrid analysis to bind the carboxy terminus of elastin microfibril ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619093 Tue, 17 Jan 2012 05:00:00 +0100 5619093 http://www.medworm.com/index.php?rid=5619095&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22242896%26dopt%3DAbstract Authors: Knöckel J, Müller IB, Butzloff S, Bergmann B, Walter RD, Wrenger C Abstract The malaria parasite Plasmodium falciparum is able to synthesize de novo pyridoxal-5-phosphate (PLP), the active form of vitamin B6. We show here that the de novo synthesized PLP is used by the parasite to detoxify singlet molecular oxygen (1O2), a highly destructive reactive oxygen species arising from hemoglobin digestion. The formation of singlet oxygen and the response of the parasite were monitored by life cell fluorescence microscopy, by transcription analysis and by determination of PLP levels in the parasite, respectively. Pull-down experiments of transgenic parasites overexpressing the vitamin B6 biosynthetic enzymes PfPdx1 and PfPdx2 clearly demonstrated an interaction of the two protei... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619095 Mon, 16 Jan 2012 05:00:00 +0100 5619095 http://www.medworm.com/index.php?rid=5619094&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22242915%26dopt%3DAbstract Authors: Barber MA, Hendrickx A, Beullens M, Ceulemans H, Oxley D, Thelen S, Thelen M, Bollen M, Welch HC Abstract P‑Rex1 is a guanine-nucleotide exchange factor (GEF) for the small G protein Rac that is activated by PIP3 and Gbg subunits and inhibited by PKA. Here, we show that Protein Phosphatase 1a (PP1a) binds P‑Rex1 through an RVxF-type docking motif. PP1a activates P‑Rex1 directly in vitro, both independently of and additively to PIP3 and Gbg. PP1a also substantially activates P‑Rex1 in vivo, both in basal and PDGF- or LPA-stimulated cells. The phosphatase activity of PP1a is required for P‑Rex1 activation. PP1b, a close homologue of PP1a, is also able to activate P‑Rex1, but less effectively. PP1a stimulates P-Rex1-mediated, Rac-dependent changes in endothelial c... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619094 Mon, 16 Jan 2012 05:00:00 +0100 5619094 http://www.medworm.com/index.php?rid=5619092&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248149%26dopt%3DAbstract In this study, we performed yeast two-hybrid screening to identify partner MAPKs for OsMKK6, a rice MAPK kinase, and revealed specific interactions of OsMKK6 with OsMPK3 and OsMPK6. OsMPK3 and OsMPK6 each co-immunoprecipitated OsMKK6, and both were directly phosphorylated by OsMKK6 in vitro. A MBP kinase assay of the immunoprecipitation complex indicated that OsMPK3 and OsMPK6 were activated in response to a moderately low temperature (12°C) but a severely low temperature (4°C) in rice seedlings. A constitutively active form of OsMKK6, OsMKK6DD, showed elevated phosphorylation activity against OsMPK3 and OsMPK6 in vitro. OsMPK3, but not OsMPK6, was constitutively activated in transgenic plants overexpressing OsMKK6DD, indicating that OsMPK3 is an in vivo target of OsMKK6. Enhanced chilli... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619092 Mon, 16 Jan 2012 05:00:00 +0100 5619092 http://www.medworm.com/index.php?rid=5619091&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248185%26dopt%3DAbstract Authors: Fukuhara A, Yamada M, Fujimori K, Miyamoto Y, Kusumoto T, Nakajima H, Inui T Abstract Lipocalin-type prostaglandin D synthase (L-PGDS) is a dual functional protein, acting as a PGD2-producing enzyme and a lipid-transporter. L-PGDS is a member of the lipocalin superfamily and can bind a wide variety of lipophilic molecules. Here we show the protective effect of L-PGDS on H2O2-induced apoptosis in neuroblastoma cell line SH-SY5Y. L-PGDS expression was increased in H2O2-treated neuronal cells, and the L-PGDS level was highly associated with H2O2-induced apoptosis, indicating that L-PGDS protected the neuronal cells against H2O2-mediated cell death. Cell viability assay revealed that L-PGDS protected against H2O2-induced cell death in a concentration-dependent manner. Further,... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619091 Mon, 16 Jan 2012 05:00:00 +0100 5619091 http://www.medworm.com/index.php?rid=5619090&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248233%26dopt%3DAbstract Authors: Cameron AR, Wallace K, Logie L, Prescott AR, Unterman TG, Harthill J, Rena G Abstract Many diseases of ageing including Alzheimer's Disease (AD) and type 2 diabetes (T2D) are strongly associated with common risk factors, such as hypertension, hyperglycaemia and hyperinsulinaemia, suggesting that there may be shared ageing mechanisms underlying these diseases, with scope to identify common cellular targets for therapy. Here we have studied insulin-like signalling properties of an experimental AD 8-hydroxyquinoline drug known as clioquinol. The insulin/IGF-1 signal transduction (IIS) kinase Akt/PKB inhibits the transcription factor FOXO1a by phosphorylating it on residues that trigger its exit from the nucleus and in 293 cells we found that clioquinol treatment induces simil... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5619090 Mon, 16 Jan 2012 05:00:00 +0100 5619090 http://www.medworm.com/index.php?rid=5544611&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22187934%26dopt%3DAbstract Authors: Lee J, Giordano S, Zhang J Abstract Reactive oxygen and nitrogen species change cellular responses through diverse mechanisms that are now being defined. At low levels, they are signalling molecules, and at high levels, they damage organelles, particularly the mitochondria. Oxidative damage and the associated mitochondrial dysfunction may result in energy depletion, accumulation of cytotoxic mediators and cell death. Understanding the interface between stress adaptation and cell death then is important for understanding redox biology and disease pathogenesis. Recent studies have found that one major sensor of redox signalling at this switch in cellular responses is autophagy. Autophagic activities are mediated by a complex molecular machinery including more than 30 Atg (Au... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5544611 Wed, 28 Dec 2011 08:36:29 +0100 5544611 http://www.medworm.com/index.php?rid=5544610&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22187935%26dopt%3DAbstract Authors: Shields MA, Dangi-Garimella S, Redig AJ, Munshi HG Abstract PDAC (pancreatic ductal adenocarcinoma) is among the most deadly of human malignances. A hallmark of the disease is a pronounced collagen-rich fibrotic extracellular matrix known as the desmoplastic reaction. Intriguingly, it is precisely these areas of fibrosis in which human PDAC tumours demonstrate increased expression of a key collagenase, MT1-MMP [membrane-type 1 MMP (matrix metalloproteinase); also known as MMP-14]. Furthermore, a cytokine known to mediate fibrosis in vivo, TGF-β1 (transforming growth factor-β1), is up-regulated in human PDAC tumours and can promote MT1-MMP expression. In the present review, we examine the regulation of PDAC progression through the interplay between type I collagen (the m... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5544610 Wed, 28 Dec 2011 08:36:21 +0100 5544610 http://www.medworm.com/index.php?rid=5544609&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22187936%26dopt%3DAbstract Authors: Romeo Y, Zhang X, Roux PP Abstract The RSK (90 kDa ribosomal S6 kinase) family comprises a group of highly related serine/threonine kinases that regulate diverse cellular processes, including cell growth, proliferation, survival and motility. This family includes four vertebrate isoforms (RSK1, RSK2, RSK3 and RSK4), and single family member orthologues are also present in Drosophila and Caenorhabditis elegans. The RSK isoforms are downstream effectors of the Ras/ERK (extracellular-signal-regulated kinase) signalling pathway. Significant advances in the field of RSK signalling have occurred in the past few years, including several new functions ascribed to the RSK isoforms, the discovery of novel protein substrates and the implication of different RSK isoforms in cancer. C... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5544609 Wed, 28 Dec 2011 08:36:12 +0100 5544609 http://www.medworm.com/index.php?rid=5506660&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22168436%26dopt%3DAbstract Authors: Magnuson B, Ekim B, Fingar DC Abstract The ribosomal protein S6K (S6 kinase) represents an extensively studied effector of the TORC1 [TOR (target of rapamycin) complex 1], which possesses important yet incompletely defined roles in cellular and organismal physiology. TORC1 functions as an environmental sensor by integrating signals derived from diverse environmental cues to promote anabolic and inhibit catabolic cellular functions. mTORC1 (mammalian TORC1) phosphorylates and activates S6K1 and S6K2, whose first identified substrate was rpS6 (ribosomal protein S6), a component of the 40S ribosome. Studies over the past decade have uncovered a number of additional S6K1 substrates, revealing multiple levels at which the mTORC1-S6K1 axis regulates cell physiology. The results ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5506660 Fri, 16 Dec 2011 12:42:42 +0100 5506660 http://www.medworm.com/index.php?rid=5506659&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22168437%26dopt%3DAbstract Authors: Mellor P, Furber LA, Nyarko JN, Anderson DH Abstract The p85α protein is best known as the regulatory subunit of class 1A PI3Ks (phosphoinositide 3-kinases) through its interaction, stabilization and repression of p110-PI3K catalytic subunits. PI3Ks play multiple roles in the regulation of cell survival, signalling, proliferation, migration and vesicle trafficking. The present review will focus on p85α, with special emphasis on its important roles in the regulation of PTEN (phosphatase and tensin homologue deleted on chromosome 10) and Rab5 functions. The phosphatidylinositol-3-phosphatase PTEN directly counteracts PI3K signalling through dephosphorylation of PI3K lipid products. Thus the balance of p85α-p110 and p85α-PTEN complexes determines the signalling output of ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5506659 Fri, 16 Dec 2011 12:42:32 +0100 5506659 http://www.medworm.com/index.php?rid=5506658&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22168438%26dopt%3DAbstract Authors: Teasdale RD, Collins BM Abstract The mammalian genome encodes 49 proteins that possess a PX (phox-homology) domain, responsible for membrane attachment to organelles of the secretory and endocytic system via binding of phosphoinositide lipids. The PX domain proteins, most of which are classified as SNXs (sorting nexins), constitute an extremely diverse family of molecules that play varied roles in membrane trafficking, cell signalling, membrane remodelling and organelle motility. In the present review, we present an overview of the family, incorporating recent functional and structural insights, and propose an updated classification of the proteins into distinct subfamilies on the basis of these insights. Almost all PX domain proteins bind PtdIns3P and are recruited to ear... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5506658 Fri, 16 Dec 2011 12:42:22 +0100 5506658 http://www.medworm.com/index.php?rid=5506657&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22168439%26dopt%3DAbstract Authors: Fleet JC, Desmet M, Johnson R, Li Y Abstract The population-based association between low vitamin D status and increased cancer risk can be inconsistent, but it is now generally accepted. These relationships link low serum 25OHD (25-hydroxyvitamin D) levels to cancer, whereas cell-based studies show that the metabolite 1,25(OH)2D (1,25-dihydroxyvitamin D) is a biologically active metabolite that works through vitamin D receptor to regulate gene transcription. In the present review we discuss the literature relevant to the molecular events that may account for the beneficial impact of vitamin D on cancer prevention or treatment. These data show that although vitamin D-induced growth arrest and apoptosis of tumour cells or their non-neoplastic progenitors are plausible mecha... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5506657 Fri, 16 Dec 2011 12:42:12 +0100 5506657 http://www.medworm.com/index.php?rid=5472094&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22122504%26dopt%3DAbstract Authors: Kleczkowski LA, Geisler M, Fitzek E, Wilczynska M PMID: 22122504 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472094 Sun, 04 Dec 2011 22:49:37 +0100 5472094 http://www.medworm.com/index.php?rid=5472093&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22122505%26dopt%3DAbstract Authors: Queiroz RF, Vaz SM, Augusto O PMID: 22122505 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472093 Sun, 04 Dec 2011 22:49:28 +0100 5472093 http://www.medworm.com/index.php?rid=5472089&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22132744%26dopt%3DAbstract Authors: Wu Y, Steinbergs N, Murray-Stewart T, Marton LJ, Casero Jr RA Abstract Epigenetic gene silencing is an important mechanism in the initiation and progression of cancer. Abnormal DNA CpG island hypermethylation and histone modifications are involved in aberrant silencing of tumor suppressor genes. Lysine-specific demethylase 1 (LSD1) was the first enzyme identified to specifically demethylate lysine 4 of histone H3 (H3K4). Methylated H3K4 is an important mark associated with transcriptional activation. The flavin adenine dinucleotide binding, amine oxidase domain of LSD1 is homologous to two polyamine oxidases, spermine oxidase and N1-acetylpolyamine oxidase. We have demonstrated that long chain polyamine analogues, the oligoamines, are inhibitors of LSD1. Here we report the... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472089 Fri, 02 Dec 2011 05:00:00 +0100 5472089 http://www.medworm.com/index.php?rid=5472088&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22132769%26dopt%3DAbstract Authors: Koschubs T, Dengl S, Duerr H, Kaluza K, Georges G, Hartl C, Jennewein S, Lanzendoerfer M, Auer J, Stern A, Huang KS, Packman K, Gubler U, Kostrewa D, Ries S, Hansen S, Kohnert U, Cramer P, Mundigl O Abstract Hepsin is a type II transmembrane serine protease that is expressed in several human tissues. Overexpression of hepsin has been found to correlate with tumor progression and metastasis, which is so far best studied for prostate cancer, where more than 90% of such tumors show this characteristic. To enable improved future patient treatment, we developed a monoclonal humanized antibody that selectively inhibits human hepsin and does not inhibit other related proteases. We found that our antibody hH35 potently inhibits hepsin enzymatic activity at nanomolar concentrations... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472088 Fri, 02 Dec 2011 05:00:00 +0100 5472088 http://www.medworm.com/index.php?rid=5472087&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22132794%26dopt%3DAbstract Authors: Andralojc PJ, Madgwick PJ, Tao Y, Keys A, Ward JL, Beale MH, Loveland JE, Jackson PJ, Willis AC, Gutteridge S, Parry MA Abstract The genes for 2-carboxy-D-arabinitol 1-phosphate phosphatase (CA1P phosphatase) from French bean, wheat, Arabidopsis and tobacco were identified and cloned. The deduced protein sequence included an N-terminal motif identical to the phosphogycerate mutase (PGM) active site sequence [LIVM]-x-R-H-G-[EQ]-x-x-[WN]. The corresponding gene from wheat coded for an enzyme with the properties published for CA1P phosphatase. The expressed protein lacked PGM activity but rapidly dephosphorylated 2,3-diphosphoglycerate to 3-phosphoglycerate. DTT activation and GSSG inactivation of this enzyme was pH sensitive, the greatest difference being apparent at pH 8. T... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472087 Fri, 02 Dec 2011 05:00:00 +0100 5472087 http://www.medworm.com/index.php?rid=5472091&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22129459%26dopt%3DAbstract Authors: Chandran S, Machamer CE Abstract The mammalian Golgi apparatus is composed of multiple stacks of cisternal membranes organized laterally into a polarized ribbon. Furthermore, trans-Golgi membranes come in close apposition with endoplasmic reticulum (ER) membranes to form ER-trans-Golgi contact sites, which may facilitate transfer of newly synthesized ceramide from the ER to sphingomyelin (SM) synthase at the trans-Golgi via ceramide transfer protein (CERT). CERT interacts with both ER and Golgi membranes, and together with Golgi morphology contributes to efficient SM synthesis. Here, we show that Golgi disassembly during proapoptotic stress induced by tumor necrosis factor (TNFa) and anisomycin results in decreased levels of CERT at the Golgi region. This is accompanied by... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472091 Thu, 01 Dec 2011 05:00:00 +0100 5472091 http://www.medworm.com/index.php?rid=5472090&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22132725%26dopt%3DAbstract Authors: Pérez-Siles G, Nunez E, Morreale A, Jiménez E, Leo-Macías A, Pita G, Cherubino F, Sangaletti R, Bossi E, Ortíz AR, Aragon C, Lopez-Corcuera B Abstract Synaptic glycine levels are controlled by glycine transporters (GLYTs). GLYT1 is the main regulator of synaptic glycine concentrations, which catalyzes Na+/Cl-/glycine cotransport with a 2:1:1 stoichiometry. By contrast, neuronal GLYT2 supplies glycine to the presynaptic terminal with a 3:1:1 stoichiometry. We subjected homology models of GLYT1 and GLYT2 to molecular dynamics simulations in the presence of Na+. Using Molecular Interaction Potential maps and in silico mutagenesis, we identified a conserved region in the GLYT2 external vestibule likely to be involved in Na+ interactions. Replacement of D471 in this region ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472090 Thu, 01 Dec 2011 05:00:00 +0100 5472090 http://www.medworm.com/index.php?rid=5472086&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22132820%26dopt%3DAbstract In conclusion, our study suggests that miR-17 plays an important role in CRC carcinogenesis by targeting RND3 and may be a therapeutic agent for CRC. PMID: 22132820 [PubMed - as supplied by publisher] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472086 Thu, 01 Dec 2011 05:00:00 +0100 5472086 http://www.medworm.com/index.php?rid=5472085&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22132858%26dopt%3DAbstract Authors: Yu Q, Zheng X Abstract UDP-glucose pyrophosphorylase (UGPase) is highly conserved among eukaryotes. UGPase reversely catalyzes the formation of UDP-glucose and is critical in carbohydrate metabolism. Previous studies have mainly focused on the UGPases from plants, fungi and parasites and indicate that the regulatory mechanisms responsible for the enzyme activity vary among different organisms. Here the crystal structure of human UGPase (hUGPase) was determined and shown to form octamers through end-to-end and side-by-side interactions. The observed latch loop in hUGPase distinctly differs from yeast UGPase (yUGPase), which could explain why hUGPase and yUGPase possess different enzymatic activities. Mutagenesis studies showed that both dissociation of octamers and mutation... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472085 Thu, 01 Dec 2011 05:00:00 +0100 5472085 http://www.medworm.com/index.php?rid=5472095&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22122405%26dopt%3DAbstract This study establishes the capacity of this Cys-Gpx to reduce peroxynitrite with a catalytic efficiency of 106 M-1 s-1. In PtGpx5, Glu79, which replaces the Gln usually found in Gpx catalytic tetrad, is likely involved in substrate selectivity. Although the redox midpoint potential of the Cys44-Cys92 disulfide and the pKa of Cys44 are not modified in the E79Q variant, it exhibited significantly improved kinetic parameters (Kperoxide and kcat) with tert-butyl hydroperoxide. The characterization of the monomeric Y151R variant demonstrated that PtGpx5 is not an obligate homodimer. Also, we show that the conserved Phe90 is important for Trx recognition and that Trx-mediated recycling of PtGpx5 occurs via the formation of a transient disulfide between the Trx catalytic cysteine and the Gpx5 res... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472095 Tue, 29 Nov 2011 05:00:00 +0100 5472095 http://www.medworm.com/index.php?rid=5472092&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22124281%26dopt%3DAbstract FUNCTIONAL MAPPING OF THE DISPARATE ACTIVITIES OF THE YEAST MOONLIGHTING PROTEIN HAL3. Biochem J. 2011 Nov 29; Authors: Abrie JA, González A, Strauss E, Ariño J Abstract The Saccharomyces cerevisiae Hal3 protein is a moonlighting protein, able to function both as an inhibitory subunit of the Ppz1 protein phosphatase and as a constituent protomer of an unprecedented heterotrimeric phosphopantothenoylcysteine decarboxylase (PPCDC), the third enzyme of the CoA biosynthetic pathway. We initiated here the dissection of the structural elements required for both disparate cellular tasks by using a combination of biochemical and genetic approaches. We show that the conserved Hal3 core (the PPCDC domain) is necessary for both functions, as determined by in vitro and in vivo assays... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5472092 Tue, 29 Nov 2011 05:00:00 +0100 5472092 http://www.medworm.com/index.php?rid=5453069&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22115042%26dopt%3DAbstract In this study, we show that the PS1-mediated (or possibly the PS2-mediated) signal is essential for the APP-mediated death in a gamma-secretase-independent manner and vice versa. MOCA (modifier of cell adhesion), originally identified as being a PS- and Rac1-binding protein, is a common downstream constituent of these neuronal death signals. The detailed molecular analysis indicates that MOCA is a key molecule of the AD-relevant neuronal death signals that links the PS-mediated death signal with the APP-mediated death signal at a point between Rac1 (or Cdc42) and ASK1. PMID: 22115042 [PubMed - as supplied by publisher] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453069 Thu, 24 Nov 2011 05:00:00 +0100 5453069 http://www.medworm.com/index.php?rid=5453068&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22115123%26dopt%3DAbstract Authors: Martin-Garcia JM, Ruiz-Sanz J, Luque I Abstract In spite of its biomedical relevance, polyproline recognition is still not fully understood. The disagreement between the current description of SH3 complexes and their thermodynamic behavior calls for a revision of the SH3 binding paradigm. Recently, Abl-SH3 was demonstrated to recognize its ligands by a dual binding mechanism involving a robust network of water-mediated hydrogen bonds that complements the canonical hydrophobic interactions. The systematic analysis of the SH3 structural database presented here reveals that this dual binding mode is universal to SH3 domains. Tightly bound, buried interfacial water molecules were found in all SH3 complexes studied mediating the interaction between the peptide ligand and the do... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453068 Thu, 24 Nov 2011 05:00:00 +0100 5453068 http://www.medworm.com/index.php?rid=5453067&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22115192%26dopt%3DAbstract We report that exposure of T47D cells to synthetic progestins (ORG2058 or Norgestrel) leads to a rapid increase in Fru-2,6-P2 concentration. Western blot results are compatible with a short-term activation due to PFKFB3 isoenzyme phosphorylation and a long-term sustained action due to increased PFKFB3 protein levels. Transient transfection of T47D cells with deleted gene promoter constructs allowed us to identify a progesterone regulatory element (PRE) to which progesterone receptor binds and thus transactivates PFKFB3 gene transcription. Progesterone Receptor (PR) expression, in the PR-negative cell line (MDA-MB-231), induces endogen PFKFB3 expression in response to Norgestrel. Direct Binding of PR to the PRE box (-3490 nt) was confirmed by ChIP experiments. A dual mechanism affecting PFK... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453067 Thu, 24 Nov 2011 05:00:00 +0100 5453067 http://www.medworm.com/index.php?rid=5453066&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22115317%26dopt%3DAbstract Authors: Pigott CR, Mikolajek H, Moore CE, Finn SJ, Phippen CW, Werner JM, Proud CG Abstract Eukaryotic elongation factor 2 kinase (eEF2K) is a calcium-calmodulin dependent protein kinase which regulates the translation elongation machinery. eEF2K belongs to the small group of so-called 'a-kinases' which are distinct from the main eukaryotic protein kinase superfamily. In addition to the a-kinase catalytic domain, other domains have been identified in eEF2K: a calmodulin-binding region, N-terminal to the kinase domain, a C-terminal region containing several predicted a-helices (resembling SEL1 domains) and a probably rather unstructured 'linker' region connecting them. Here, we demonstrate (i) that several highly conserved residues, implicated in binding ATP or metal ions, are crit... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453066 Thu, 24 Nov 2011 05:00:00 +0100 5453066 http://www.medworm.com/index.php?rid=5453070&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103330%26dopt%3DAbstract This study provides support for BAD-Ser170 phosphorylation playing a key role not only in regulating BAD's pro-apoptotic activity, but also its role in cell proliferation. PMID: 22103330 [PubMed - as supplied by publisher] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453070 Tue, 22 Nov 2011 05:00:00 +0100 5453070 http://www.medworm.com/index.php?rid=5453071&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22103299%26dopt%3DAbstract This study focuses on the effect of mhtt on the subcellular localization of glutamic acid decarboxylase (GAD), the enzyme responsible for synthesizing GABA. In this study, we report that the subcellular distribution of GAD is significantly altered in two neuronal cell lines that express either the N-terminus or full length mhtt. GAD65 is predominantly associated with Golgi membrane in cells expressing normal htt. However, it diffuses in the cytosol of cells expressing mhtt. As a result, vesicle-associated GAD65 trafficking is impaired. Since palmitoylation of GAD65 is required for GAD65 trafficking, we then demonstrate that palmitoylation of GAD65 is reduced in the HD model. Furthermore, overexpression of huntingtin-interacting protein 14, the enzyme responsible for palmitoylating GAD65 in... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453071 Mon, 21 Nov 2011 05:00:00 +0100 5453071 http://www.medworm.com/index.php?rid=5453072&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22091998%26dopt%3DAbstract In this study, we first purified vWF from HD-patients and then chemically characterized its oxidative state. Interestingly, HD-vWF contains high carbonyl levels and increased proportion of UL-vWF polymers, which are also more resistant to ADAMTS-13. Using targeted mass spectrometry techniques, we estimated that HD-vWF contains <10% of Met1606 in the sulphoxide form. We conclude that oxidation of Met1606, impairing ADAMTS-13 cleavage, results in the accumulation of UL-vWF polymers, which recruit and activate more efficiently platelets and bind more tightly to bacterial adhesins, thus contributing to the development of thrombotic and septic complications in CKD. PMID: 22091998 [PubMed - as supplied by publisher] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453072 Fri, 18 Nov 2011 05:00:00 +0100 5453072 http://www.medworm.com/index.php?rid=5453074&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22087554%26dopt%3DAbstract In this study, we provide evidence that rOrf8/EscI, a poorly characterized locus of enterocyte effacement-encoded protein, functions as the inner rod protein of the T3SS of enteropathogenic E. coli (EPEC). We demonstrated that EscI is essential for type III secretion and is also secreted as an early substrate of the T3SS. We found that EscI interacts with EscU, the integral membrane protein that is linked to substrate specificity switching, implicating EscI in the substrate-switching event. Furthermore, we showed that EscI self-associates and interacts with the outer membrane secretin, EscC, further supporting its function as an inner rod protein. Overall, our data suggest that EscI is the YscI/PrgJ/MxiI homolog in the T3SS of attaching and effacing pathogens. . PMID: 22087554 [PubMed... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453074 Thu, 17 Nov 2011 05:00:00 +0100 5453074 http://www.medworm.com/index.php?rid=5453073&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22091967%26dopt%3DAbstract This study focuses on the A13T (alanine to threonine) mutation in the human ventricular myosin regulatory light chain (RLC) that is associated with a rare FHC variant defined by mid ventricular obstruction and septal hypertrophy. Here, we generated heart specific transgenic (Tg) mice with ~10% of human A13T-RLC mutant replacing the endogenous mouse cardiac RLC. Histopathological examinations of longitudinal heart sections from Tg-A13T mice showed enlarged inter-ventricular septa and profound fibrotic lesions compared to Tg-WT, expressing the human ventricular RLC, or to non-Tg mice. Functional studies revealed an abnormal A13T-induced increase in isometric force production, no change in the force-pCa relationship and a decreased Vmax of the acto-myosin ATPase. In addition, a fluorescence-b... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453073 Thu, 17 Nov 2011 05:00:00 +0100 5453073 http://www.medworm.com/index.php?rid=5453076&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22084935%26dopt%3DAbstract Authors: Marttila M, Lemola E, Wallefeld W, Memo M, Donner K, Laing NG, Marston S, Grönholm M, Wallgren-Pettersson C Abstract Nemaline myopathy (NM) is a rare, genetic muscle disorder defined on the basis of muscle weakness and the presence of structural abnormalities in the muscle fibres, i.e. nemaline bodies. The related disorder cap myopathy is defined by cap-like structures located peripherally in the muscle fibres. Both disorders may be caused by mutations in the TPM2 gene encoding beta-tropomyosin (Tm). Tm controls muscle contraction by inhibiting actin-myosin interaction in a calcium sensitive manner. We have studied the pathogenetic mechanisms underlying six disease causing mutations in Tm. We show that five of the mutations cause changes in affinity for actin, which may c... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453076 Wed, 16 Nov 2011 05:00:00 +0100 5453076 http://www.medworm.com/index.php?rid=5453075&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22084975%26dopt%3DAbstract In this study we demonstrate that the periplasmic protein ZraP contributes to envelope homeostasis and assign both chaperone and regulatory function to ZraP purified from Salmonella Typhimurium. The ZraP chaperone mechanism is catalytic and independent of ATP; the chaperone activity is dependent on the presence of zinc, which is shown to be responsible for the stabilisation of an oligomeric ZraP complex. Furthermore, ZraP can act to repress the two component regulatory system ZraSR, which itself is responsive to zinc concentrations. Through structural homology, ZraP is a member of the bacterial CpxP family of periplasmic proteins, which also consists of CpxP and Spy. We demonstrate environmental co-expression of the CpxP family and identify an important role for these proteins in Salmon... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5453075 Tue, 15 Nov 2011 05:00:00 +0100 5453075 http://www.medworm.com/index.php?rid=5412177&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082005%26dopt%3DAbstract Authors: Bickford JS, Newsom KJ, Herlihy JD, Muller C, Keeler B, Qiu X, Walters JN, Su N, Wallet SM, Flotte TR, Nick HS Abstract Airway inflammation in allergen-induced asthma is associated with eicosanoid release. These bioactive lipids exhibit anti- and pro-inflammatory activities with relevance to pulmonary pathophysiology. We hypothesized that sensitization/challenge using an extract from the ubiquitous fungus, Aspergillus fumigatus (Af), in a mouse model of allergic asthma would result in altered phospholipase gene expression, thus modulating the downstream eicosanoid pathway. We observed the most significant induction in the group IVC phospholipase A2 (cPLA2γ or PLA2G4C). Our results infer that Af extract can induce cPLA2γ levels directly in eosinophils while induction in l... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412177 Tue, 15 Nov 2011 05:00:00 +0100 5412177 http://www.medworm.com/index.php?rid=5412176&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082028%26dopt%3DAbstract In this study we have obtained the 41 transcripts encoding proteins by RT-PCR using RNA template from Drosophila S2 cells, an embryonic cell line. This observation suggests that all the annotated DmGSTs in the proteome are expressed in the late embryonic stages of Drosophila melanogaster. To avoid confusion in naming these numerous DmGSTs, we have designated them following the universal GST nomenclature as well as previous designations that fit within this classification. Furthermore, in the cell line, we identified an apparent processed pseudogene, gste8; in addition to 2 isoforms from Delta class that have been previously published. Only about one third of the expressed DmGSTs could be purified by conventional GSH affinity chromatography. The diverse kinetic properties as well as physiol... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412176 Tue, 15 Nov 2011 05:00:00 +0100 5412176 http://www.medworm.com/index.php?rid=5412179&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22077489%26dopt%3DAbstract Authors: Chuai Y, Gao F, Li B, Zhao L, Qian L, Cao F, Wang L, Sun X, Cui J, Cai J Abstract Recent studies of our department suggest that hydrogen (H2) has a potential as a novel radioprotector without known toxic side effects. This paper was designed to study the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, we identified the free radical species that H2 reduced was hydroxyl radicals (•OH). We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein, however, as we treated the mice with H2 after irradiation, the descent is not significant. We found pretreatment of H2 to ionizi... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412179 Mon, 14 Nov 2011 05:00:00 +0100 5412179 http://www.medworm.com/index.php?rid=5412178&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22081970%26dopt%3DAbstract Authors: Darvekar S, Johnsen SS, Eriksen AB, Johansen T, Sjøttem E Abstract Transcriptional regulation requires coordinated action of transcription factors, co-activator complexes and general transcription factors to access specific loci in the dense chromatin structure. Here we demonstrate that the transcriptional co-regulator Stromelysin-1 PDGF responsive element binding protein (SPBP) contains two independent chromatin binding domains, the SPBP(1551-1666) region and the C-terminal extended PHD (ePHD/ADD) domain. The region 1551-1666 is a novel core nucleosome interaction domain located adjacent to the AT-hook motif in the DNA binding domain. This novel nucleosome binding region is critically important for proper localisation of SPBP in the cell nucleus. The ePHD/ADD domain asso... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412178 Mon, 14 Nov 2011 05:00:00 +0100 5412178 http://www.medworm.com/index.php?rid=5412180&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22077443%26dopt%3DAbstract This study provides intriguing insights into the molecular details of LOX-1 recognition of OxLDL. PMID: 22077443 [PubMed - as supplied by publisher] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412180 Fri, 11 Nov 2011 05:00:00 +0100 5412180 http://www.medworm.com/index.php?rid=5412306&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22070099%26dopt%3DAbstract Authors: Broniowska KA, Keszler A, Basu S, Kim-Shapiro DB, Hogg N Abstract S-Nitrosothiols are products of nitric oxide metabolism that have been implicated in a plethora of signaling processes. However, mechanisms of S-nitrosothiol formation in biological systems are uncertain and no efficient protein-mediated process has been identified. Recently, we observed that ferric cytochrome c can promote S-nitrosoglutathione formation from nitric oxide and glutathione by acting as an electron acceptor under anaerobic conditions. In the current study we show that this mechanism also is robust under oxygenated conditions, that cytochrome c can promote protein S-nitrosation via a transnitrosation reaction, and that cell lysate depleted of cytochrome c exhibits lower capacity to synthesize S-... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412306 Thu, 10 Nov 2011 05:00:00 +0100 5412306 http://www.medworm.com/index.php?rid=5412293&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22070140%26dopt%3DAbstract Authors: Origanti S, Nowotarski SL, Carr TD, Sass-Kuhn S, Xiao L, Wang JY, Shantz LM Abstract Upon ras activation, ornithine decarboxylase (ODC) is markedly induced, and numerous studies suggest that ODC expression is controlled by Ras effector pathways. ODC is therefore a potential target in the treatment and prevention of Ras-driven tumors. We compared ODC mRNA translation profiles and stability in normal and Ras12V-transformed rat intestinal epithelial (RIE-1) cells. While translation initiation of ODC increased modestly in Ras12V cells, ODC RNA was stabilized 8-fold. Treatment with the specific mTORC1 inhibitor rapamycin or siRNA knockdown of mTOR destabilized the ODC message, but rapamycin had only a minor effect on ODC translation initiation. Inhibition of mTORC1 also reduced... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412293 Thu, 10 Nov 2011 05:00:00 +0100 5412293 http://www.medworm.com/index.php?rid=5412229&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22070190%26dopt%3DAbstract THE PH-SENSOR OF THE PLANT K+ UPTAKE CHANNEL KAT1 IS BUILT OF A SENSORY CLOUD RATHER THAN OF SINGLE KEY AMINO ACIDS. Biochem J. 2011 Nov 10; Authors: Gonzalez W, Riedelsberger J, Morales-Navarro SE, Caballero J, Alzate-Morales JH, González-Nilo FD, Dreyer I Abstract The uptake of potassium ions (K+) accompanied by an acidification of the apoplasm is a prerequisite for stomatal opening. The acidification (around 2-2.5 pH units) is perceived by voltage gated inward potassium channels (Kin) that then can open their pores with lower energy cost. The sensory units for extracellular pH in stomatal Kin channels are proposed to be histidines exposed to the apoplasm. However, in the Arabidopsis thaliana stomatal Kin channel KAT1, mutations in the unique histidine (H267) exposed to ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412229 Thu, 10 Nov 2011 05:00:00 +0100 5412229 http://www.medworm.com/index.php?rid=5412181&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22070747%26dopt%3DAbstract Authors: Oliveri LM, Davio C, Batlle AM, Gerez EN Abstract Porphyrias are diseases caused by partial deficiencies of haem biosynthesis enzymes. Acute porphyrias are characterized by a neuropsychiatric syndrome with intermittent induction of hepatic δ-aminolevulinate synthase 1 (ALAS-1), first and rate-limiting enzyme of haem pathway. Porphyria acute attacks are usually treated with glucose administration, its effect is apparently related to its ability of inhibiting ALAS-1 by modulating insulin plasma levels. It was shown that insulin blunts hepatocytes ALAS-1 induction, by disrupting the interaction of the Forkhead box O1 (FOXO1) and the proliferator-activated receptor γ coactivator 1α (PGC-1α). We evaluated the expression of ALAS-1 in a murine model of diabetes and determined... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412181 Thu, 10 Nov 2011 05:00:00 +0100 5412181 http://www.medworm.com/index.php?rid=5412182&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22070227%26dopt%3DAbstract Recruitment of the endosomal WASH complex is mediated by the extended "tail" of Fam21 binding to the retromer protein VPS35. Biochem J. 2011 Nov 9; Authors: Harbour ME, Breusegem SY, Seaman MN Abstract The retromer complex is a conserved endosomal protein sorting complex that sorts membrane proteins into nascent endosomal tubules. The recognition of membrane proteins is mediated by the cargo-selective retromer complex, a stable trimer of the VPS35, VPS29 and VPS26 proteins. We have recently reported that the cargo-selective retromer complex associates with the WASH complex, a multimeric protein complex that regulates tubule dynamics at endosomes. Here we show that the retromer-WASH complex interaction occurs through the long unstructured "tail" domain of the WASH complex-Fa... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412182 Wed, 09 Nov 2011 05:00:00 +0100 5412182 http://www.medworm.com/index.php?rid=5412309&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22060158%26dopt%3DAbstract This study examines the role of QC-mediated pGlu formation on monocyte chemoattractant proteins (MCPs) in inflammation. We demonstrated in vitro the pGlu formation on MCPs by QC using mass spectrometry. A potent QC inhibitor, PBD150, significantly reduced the N-terminal uncyclized MCPs precursor (preMCPs)-stimulated monocyte migration, whereas pGlu-containing MCPs (pMCPs)-induced cell migration was unaffected. QC siRNA revealed a similar inhibitory effect. Lastly, we demonstrated that inhibiting QC can attenuate cell migration by LPS. These results strongly suggest that QC-catalyzed N-terminal pGlu formation of MCPs is required for monocyte migration, and provide new insights into the role of QC in the inflammation process. Our results also suggest that QC could be a drug target for some i... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412309 Tue, 08 Nov 2011 05:00:00 +0100 5412309 http://www.medworm.com/index.php?rid=5412308&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22060242%26dopt%3DAbstract This study describes AGE inhibition and the mechanism of action of new antiglycating agent, ellagic acid (EA), a flavonoid present in many dietary sources. Inhibition of AGE formation by EA was demonstrated with different proteins viz eye lens total soluble protein (TSP), hemoglobin (Hb), lysozyme and BSA using divergent glycating agents like fructose, ribose and methylglyoxal by a set of complementary methods. These results suggest that antiglycating action of EA seems to involve, apart from the inhibition of a few fluorescent AGE, predominantly inhibition of Nε-(carboxyethyl)lysine (CEL) through scavenging of dicarbonyl compounds. Further, MALDI-ToF/ToF analysis confirms inhibition of formation of CEL on lysozyme upon in vitro glycation by EA. Prevention of glycation-mediated β-sheet f... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412308 Tue, 08 Nov 2011 05:00:00 +0100 5412308 http://www.medworm.com/index.php?rid=5412307&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22060312%26dopt%3DAbstract Authors: Marcos-Almaraz MT, Rodriguez-Gomez JA, Lopez-Barneo J, Pascual A Abstract Discovery of hemoglobin A expression outside of the erythroid cell lineage suggests that oxygen transport is the main but not the unique function of adult hemoglobin chains in mammalians. The contribution of hemoglobin A to antioxidant defenses has been proposed in the territories where it is expressed. Catecholaminergic cells relay on an active oxidative metabolism to accomplish their biological function but are exposed to strong oxidative stress due to metabolism of catecholaminergic transmitters. We show here that peripheral catecholaminegic cells express the alpha and not the beta hemoglobin A chains and that alpha-hemoglobin expression could modulate the antioxidant capabilities of these cells. ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412307 Tue, 08 Nov 2011 05:00:00 +0100 5412307 http://www.medworm.com/index.php?rid=5412310&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22054284%26dopt%3DAbstract Authors: Shymanets A, Ahmadian MR, Koessmeier KT, Wetzker R, Harteneck C, Nürnberg B Abstract G-protein-regulated phosphoinositide 3-kinase g (PI3Kg) plays a crucial role in inflammatory and allergic processes. PI3Kγ, a dimeric protein formed by non-catalytic p101 and catalytic p110γ subunits, is stimulated by receptor-released Gbg complexes. We previously demonstrated that Gbg stimulates both monomeric p110g and dimeric p110g/p101 lipid kinase activity in vitro. In order to identify the Gb residues responsible for the Gbg-PI3Kg-interaction, we examined Gb1 mutants for their ability to stimulate lipid and protein kinase activities and to recruit PI3Kg to lipid vesicles. Our findings revealed different interaction profiles of Gβ residues interacting with p110g or p110g/p101. Mor... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412310 Mon, 07 Nov 2011 05:00:00 +0100 5412310 http://www.medworm.com/index.php?rid=5412311&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22054235%26dopt%3DAbstract Authors: Roszak AW, Moulisova V, Reksodipuro AD, Gardiner AT, Fujii R, Hashimoto H, Isaacs NW, Cogdell RJ Abstract Newly determined crystal structures of the photosynthetic reaction centre (RC) from two substrains of the non-sulphur purple bacterium Blastochloris viridis strain DSM 133, together with analysis of their gene sequences, has revealed intra-species evolutionary changes over a time period of 14 years. Over one hundred point mutations were identified between these two substrains in the four genes encoding the protein subunits of the RC, of which about one fifth resulted in a total of 16 amino acid changes. The most interesting difference was in the M subunit where the change from leucine to glycine in the carotenoid binding pocket allowed dihydroneurosporene to adopt a mo... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412311 Fri, 04 Nov 2011 04:00:00 +0100 5412311 http://www.medworm.com/index.php?rid=5412312&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22050124%26dopt%3DAbstract In conclusion, due to its pH sensitivity, mt-HyPer is not a reliable indicator of mitochondrial hydrogen peroxide in β-cells. In contrast, mt-roGFP1 fluorescence ratio monitors changes in β-cell mitochondrial glutathione redox state with little interference by pH changes. Our results also show that glucose acutely decreases rather than increases mitochondrial thiol oxidation in rat β-cells. PMID: 22050124 [PubMed - as supplied by publisher] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5412312 Thu, 03 Nov 2011 04:00:00 +0100 5412312 http://www.medworm.com/index.php?rid=5376807&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22047502%26dopt%3DAbstract Authors: Ito G, Iwatsubo T Abstract Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified in PARK8, a major form of autosomal-dominantly inherited familial Parkinson's disease, although the biochemical properties of LRRK2 are not fully understood. Recent reports proposed that LRRK2 predominantly exists as a homodimer based on the observation that LRRK2, with a theoretical mass of 280 kDa, migrates at 600 kDa position (p600 LRRK2) on native polyacrylamide gels. Here, we biochemically re-examined the nature of p600 LRRK2 and found that the p600 LRRK2 was fractionated with a single peak at ~272 kDa by ultracentrifugation on a glycerol gradient. In addition, the p600 LRRK2 behaved similarly to monomeric proteins upon two-dimensional electrophoretic separation.... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5376807 Wed, 02 Nov 2011 04:00:00 +0100 5376807 http://www.medworm.com/index.php?rid=5376809&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22039967%26dopt%3DAbstract Authors: Rowley G, Hensen D, Felgate H, Arkenberg A, Appia-Ayme C, Prior K, Harrington C, Field SJ, Butt JN, Baggs E, Richardson DJ Abstract The production of cytoxic nitric oxide (NO) and conversion to the neuropharmacological agent and potent greenhouse gas nitrous oxide (N2O) is linked with anoxic nitrate catabolism by Salmonella enterica serovar Typhimurium. Salmonella can synthesize two types of nitrate reductase, a membrane-bound form (Nar) and a periplasmic form (Nap). Nitrate catabolism was studied under nitrate-rich and nitrate-limited conditions in chemostat cultures following transition from oxic to anoxic conditions. Intracellular NO production was reported qualitatively by assessing transcription of the NO-regulated genes encoding flavohemoglobin (Hmp), flavorubredoxin... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5376809 Tue, 01 Nov 2011 04:00:00 +0100 5376809 http://www.medworm.com/index.php?rid=5376808&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22044397%26dopt%3DAbstract Authors: Bourbonais FJ, Chen J, Huang C, Zhang Y, Pfefferkorn JA, Landro JA Abstract Glucokinase is an enzyme central to glucose metabolism that displays positive cooperativity to substrate glucose. Small molecule glucokinase activators (GKAs) modulate GK catalytic activity and glucose affinity and are currently being pursued as a treatment for type 2 diabetes. GK progress curves monitoring product formation are linear up to 1 mM glucose, but biphasic at 5 mM, with the transition from the lower initial velocity to the higher steady-state velocity being described by a rate constant kact. In the presence of a liver-specific GKA (Compound A), progress curves at 1 mM glucose are similar to those at 5 mM, reflecting activation of GK by Compound A. We show that GK regulatory protein (GKR... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5376808 Tue, 01 Nov 2011 04:00:00 +0100 5376808 http://www.medworm.com/index.php?rid=5324083&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21992097%26dopt%3DAbstract Authors: Morgan AJ, Platt FM, Lloyd-Evans E, Galione A Abstract Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In pa... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5324083 Tue, 18 Oct 2011 05:00:36 +0100 5324083 http://www.medworm.com/index.php?rid=5324082&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21992098%26dopt%3DAbstract Authors: Kleczkowski LA, Geisler M, Fitzek E, Wilczynska M Abstract Plant pyrophosphorylases that are capable of producing UDP-sugars, key precursors for glycosylation reactions, include UDP-glucose pyrophosphorylases (A- and B-type), UDP-sugar pyrophosphorylase and UDP-N-acetylglucosamine pyrophosphorylase. Although not sharing significant homology at the amino acid sequence level, the proteins share a common structural blueprint. Their structures are characterized by the presence of the Rossmann fold in the central (catalytic) domain linked to enzyme-specific N-terminal and C-terminal domains, which may play regulatory functions. Molecular mobility between these domains plays an important role in substrate binding and catalysis. Evolutionary relationships and the role of (de)olig... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5324082 Tue, 18 Oct 2011 05:00:25 +0100 5324082 http://www.medworm.com/index.php?rid=5324081&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21992099%26dopt%3DAbstract Authors: Boslem E, Macintosh G, Preston AM, Bartley C, Busch AK, Fuller M, Laybutt DR, Meikle PJ, Biden TJ PMID: 21992099 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5324081 Tue, 18 Oct 2011 05:00:14 +0100 5324081 http://www.medworm.com/index.php?rid=5272855&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707535%26dopt%3DAbstract Authors: Järvi S, Suorsa M, Paakkarinen V, Aro EM Abstract Gel-based analysis of thylakoid membrane protein complexes represents a valuable tool to monitor the dynamics of the photosynthetic machinery. Native-PAGE preserves the components and often also the conformation of the protein complexes, thus enabling the analysis of their subunit composition. Nevertheless, the literature and practical experimentation in the field sometimes raise confusion owing to a great variety of native-PAGE and thylakoid-solubilization systems. In the present paper, we describe optimized methods for separation of higher plant thylakoid membrane protein complexes by native-PAGE addressing particularly: (i) the use of detergent; (ii) the use of solubilization buffer; and (iii) the gel electrophoresis me... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272855 Sun, 02 Oct 2011 22:42:31 +0100 5272855 http://www.medworm.com/index.php?rid=5272854&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21711244%26dopt%3DAbstract Authors: McCallum M, Shaw GS, Creuzenet C Abstract The capsule of Campylobacter jejuni strain 81-176 comprises the unusual 6-deoxy-α-D-altro-heptose, whose biosynthesis and function are not known. In the present study, we characterized enzymes of the capsular cluster, WcbK and WcaG, to determine their role in 6-deoxy-altro-heptose synthesis. These enzymes are similar to the Yersinia pseudotuberculosis GDP-manno-heptose dehydratase/reductase DmhA/DmhB that we characterized previously. Capillary electrophoresis and MS analyses showed that WcbK is a GDP-manno-heptose dehydratase whose product can be reduced by WcaG, and that WcbK/WcaG can use the substrate GDP-mannose, although with lower efficiency than heptose. Comparison of kinetic parameters for WcbK and DmhA indicated that the r... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272854 Sun, 02 Oct 2011 22:42:19 +0100 5272854 http://www.medworm.com/index.php?rid=5272853&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726196%26dopt%3DAbstract Authors: Obi IR, Nordfelth R, Francis MS Abstract Periplasmic PPIases (peptidylprolyl cis-trans isomerases) catalyse the cis-trans isomerization of peptidyl-prolyl bonds, which is a rate-limiting step during protein folding. We demonstrate that the surA, ppiA, ppiD, fkpA and fklB alleles each encode a periplasmic PPIase in the bacterial pathogen Yersinia pseudotuberculosis. Of these, four were purified to homogeneity. Purified SurA, FkpA and FklB, but not PpiD, displayed detectable PPIase activity in vitro. Significantly, only Y. pseudotuberculosis lacking surA caused drastic alterations to the outer membrane protein profile and FA (fatty acid) composition. They also exhibited aberrant cellular morphology, leaking LPS (lipopolysaccharide) into the extracellular environment. The Sur... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272853 Sun, 02 Oct 2011 22:42:07 +0100 5272853 http://www.medworm.com/index.php?rid=5272852&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726201%26dopt%3DAbstract We report in the present paper that targeted inactivation of Slc7a8 leads to increased urinary loss of small neutral amino acids. Development and growth of Slc7a8-/- mice appears normal, suggesting functional compensation of neutral amino acid transport by alternative transporters in kidney, intestine and placenta. Movement co-ordination is slightly impaired in mutant mice, although cerebellar development and structure remained inconspicuous. Circulating thyroid hormones, thyrotropin and thyroid hormone-responsive genes remained unchanged in Slc7a8-/- mice, possibly because of functional compensation by the thyroid hormone transporter Mct8 (monocarboxylate transporter 8), which is co-expressed in many cell types. The reason for the mild neurological phenotype remains unresolved. PMID: ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272852 Sun, 02 Oct 2011 22:41:56 +0100 5272852 http://www.medworm.com/index.php?rid=5272851&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21728993%26dopt%3DAbstract Authors: Romá-Mateo C, Solaz-Fuster Mdel C, Gimeno-Alcañiz JV, Dukhande VV, Donderis J, Worby CA, Marina A, Criado O, Koller A, Rodriguez De Cordoba S, Gentry MS, Sanz P Abstract Lafora progressive myoclonus epilepsy [LD (Lafora disease)] is a fatal autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in either the EPM2A gene, encoding the dual-specificity phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Previously, we and others showed that laforin and malin form a functional complex that regulates multiple aspects of glycogen metabolism, and that the interaction between laforin and malin is enhanced by conditions activating AMPK (AMP-activated protein kinase). In the present study, we demonstrate that laforin is a ph... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272851 Sun, 02 Oct 2011 22:41:45 +0100 5272851 http://www.medworm.com/index.php?rid=5272850&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21728995%26dopt%3DAbstract Authors: Wang B, Peng Y, Zhang T, Ding J Abstract GSTs (glutathione transferases) are a family of enzymes that primarily catalyse nucleophilic addition of the thiol of GSH (reduced glutathione) to a variety of hydrophobic electrophiles in the cellular detoxification of cytotoxic and genotoxic compounds. GSTks (Kappa class GSTs) are a distinct class because of their unique cellular localization, function and structure. In the present paper we report the crystal structures of hGSTk (human GSTk) in apo-form and in complex with GTX (S-hexylglutathione) and steady-state kinetic studies, revealing insights into the catalytic mechanism of hGSTk and other GSTks. Substrate binding induces a conformational change of the active site from an 'open' conformation in the apo-form to a 'closed' co... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272850 Sun, 02 Oct 2011 22:41:35 +0100 5272850 http://www.medworm.com/index.php?rid=5272849&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21729003%26dopt%3DAbstract Authors: Busch AW, Reijerse EJ, Lubitz W, Frankenberg-Dinkel N, Hofmann E Abstract PEB (phycoerythrobilin) is one of the major open-chain tetrapyrrole molecules found in cyanobacterial light-harvesting phycobiliproteins. In these organisms, two enzymes of the ferredoxin-dependent bilin reductase family work in tandem to reduce BV (biliverdin IXα) to PEB. In contrast, a single cyanophage-encoded enzyme of the same family has been identified to catalyse the identical reaction. Using UV-visible and EPR spectroscopy we investigated the two individual cyanobacterial enzymes PebA [15,16-DHBV (dihydrobiliverdin):ferredoxin oxidoreductase] and PebB (PEB:ferredoxin oxidoreductase) showing that the two subsequent reactions catalysed by the phage enzyme PebS (PEB synthase) are clearly dissec... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272849 Sun, 02 Oct 2011 22:41:24 +0100 5272849 http://www.medworm.com/index.php?rid=5272848&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21732909%26dopt%3DAbstract Authors: Vandenberg RJ, Handford CA, Campbell EM, Ryan RM, Yool AJ Abstract Glutamate transport is coupled to the co-transport of 3 Na+ and 1 H+ followed by the counter-transport of 1 K+. In addition, glutamate and Na+ binding to glutamate transporters generates an uncoupled anion conductance. The human glial glutamate transporter EAAT1 (excitatory amino acid transporter 1) also allows significant passive and active water transport, which suggests that water permeation through glutamate transporters may play an important role in glial cell homoeostasis. Urea also permeates EAAT1 and has been used to characterize the permeation properties of the transporter. We have previously identified a series of mutations that differentially affect either the glutamate transport process or the s... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272848 Sun, 02 Oct 2011 22:41:13 +0100 5272848 http://www.medworm.com/index.php?rid=5272846&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767261%26dopt%3DAbstract Authors: Romero Rosales K, Singh G, Wu K, Chen J, Janes MR, Lilly MB, Peralta ER, Siskind LJ, Bennett MJ, Fruman DA, Edinger AL Abstract Cancer cells are hypersensitive to nutrient limitation because oncogenes constitutively drive glycolytic and TCA (tricarboxylic acid) cycle intermediates into biosynthetic pathways. As the anaplerotic reactions that replace these intermediates are fueled by imported nutrients, the cancer cell's ability to generate ATP becomes compromised under nutrient-limiting conditions. In addition, most cancer cells have defects in autophagy, the catabolic process that provides nutrients from internal sources when external nutrients are unavailable. Normal cells, in contrast, can adapt to the nutrient stress that kills cancer cells by becoming quiescent and ca... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272846 Sun, 02 Oct 2011 22:41:03 +0100 5272846 http://www.medworm.com/index.php?rid=5272838&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21806543%26dopt%3DAbstract Authors: Cameron AJ, Linch MD, Saurin AT, Escribano C, Parker PJ Abstract The protein kinase TOR (target of rapamycin) is a key regulator of cell growth and metabolism with significant clinical relevance. In mammals, TOR signals through two distinct multi-protein complexes, mTORC1 and mTORC2 (mammalian TOR complex 1 and 2 respectively), the subunits of which appear to define the operational pathways. Rapamycin selectively targets mTORC1 function, and the emergence of specific ATP-competitive kinase inhibitors has enabled assessment of dual mTORC1 and mTORC2 blockade. Little is known, however, of the molecular action of mTORC2 components or the relative importance of targeting this pathway. In the present study, we have identified the mTORC2 subunit Sin1 as a direct binding partner ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272838 Sun, 02 Oct 2011 22:40:53 +0100 5272838 http://www.medworm.com/index.php?rid=5272837&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21954942%26dopt%3DAbstract Authors: Gaboriaud C, Gregory-Pauron L, Teillet F, Thielens NM, Bally I, Arlaud GJ Abstract CUB domains are 110-residue protein motifs exhibiting a β-sandwich fold and mediating protein-protein interactions in various extracellular proteins. Recent X-ray structural and mutagenesis studies have led to the identification of a particular CUB domain subset, cbCUB (Ca2+-binding CUB domain). Unlike other CUB domains, these harbour a homologous Ca2+-binding site that underlies a conserved binding site mediating ionic interaction between two of the three conserved acidic Ca2+ ligands and a basic (lysine or arginine) residue of a protein ligand, similar to the interactions mediated by the low-density lipoprotein receptor family. cbCUB-mediated protein-ligand interactions usually involve mu... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272837 Sun, 02 Oct 2011 22:40:43 +0100 5272837 http://www.medworm.com/index.php?rid=5272836&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21954943%26dopt%3DAbstract Authors: Subbaiah VK, Kranjec C, Thomas M, Banks L Abstract Over 250 PDZ (PSD95/Dlg/ZO-1) domain-containing proteins have been described in the human proteome. As many of these possess multiple PDZ domains, the potential combinations of associations with proteins that possess PBMs (PDZ-binding motifs) are vast. However, PDZ domain recognition is a highly specific process, and much less promiscuous than originally thought. Furthermore, a large number of PDZ domain-containing proteins have been linked directly to the control of processes whose loss, or inappropriate activation, contribute to the development of human malignancies. These regulate processes as diverse as cytoskeletal organization, cell polarity, cell proliferation and many signal transduction pathways. In the present re... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272836 Sun, 02 Oct 2011 22:40:33 +0100 5272836 http://www.medworm.com/index.php?rid=5272835&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21954944%26dopt%3DAbstract Authors: Bröer S Abstract Metabolism in tumour cells is adapted to the demands of a growing cell. The Warburg effect and increased use of glutamine are two well-known adaptations of tumour metabolism. Both require transporters to allow uptake of substrates and efflux of products. Differentiated cells are less reliant on these pathways and as a result are less vulnerable to drugs that curtail nutrient uptake. Thus drugs that reduce nutrient uptake are promising candidates for tumour therapy. Detailed understanding of tumour cell biology will allow the generation of new chemotherapeutic drugs with limited side effects. PMID: 21954944 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272835 Sun, 02 Oct 2011 22:40:23 +0100 5272835 http://www.medworm.com/index.php?rid=5272834&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21957963%26dopt%3DAbstract Authors: Winzor DJ Abstract The publication of two articles by Pat Andrews on the estimation of protein molecular masses by gel filtration sparked a frenzy of interest and activity in the 1960s, an era marked by a pronounced shift in emphasis of biochemical research towards an understanding of biology at the molecular level. Unlike many research fashions, this one has flourished for the best part of 50 years and shows no sign of abating. In that period the first of those articles has attracted almost 5000 citations, and the second is approaching the 4000 mark: numbers which place both papers in the top-ten most cited Biochemical Journal articles. Their consideration as BJ Classics is thus well merited. PMID: 21957963 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5272834 Sun, 02 Oct 2011 22:40:03 +0100 5272834 http://www.medworm.com/index.php?rid=5225808&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21916843%26dopt%3DAbstract Authors: Gadalla KK, Bailey ME, Cobb SR Abstract Mutations in the X-linked gene MECP2 (methyl CpG-binding protein 2) are the primary cause of the neurodevelopmental disorder RTT (Rett syndrome), and are also implicated in other neurological conditions. The expression product of this gene, MeCP2, is a widely expressed nuclear protein, especially abundant in mature neurons of the CNS (central nervous system). The major recognized consequences of MECP2 mutation occur in the CNS, but there is growing awareness of peripheral effects contributing to the full RTT phenotype. MeCP2 is classically considered to act as a DNA methylation-dependent transcriptional repressor, but may have additional roles in regulating gene expression and chromatin structure. Knocking out Mecp2 function in mice ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5225808 Sun, 18 Sep 2011 01:43:03 +0100 5225808 http://www.medworm.com/index.php?rid=5225807&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21916844%26dopt%3DAbstract Authors: Tsai CJ, Nussinov R Abstract How is specificity transmitted over long distances at the molecular level? REs (regulatory elements) are often far from transcription start sites. In the present review we discuss possible mechanisms to explain how information from specific REs is conveyed to the basal transcription machinery through TFs (transcription factors) and the Mediator complex. We hypothesize that this occurs through allosteric pathways: binding of a TF to a RE results in changes in the AD (activation domain) of the TF, which binds to Mediator and alters the distribution of the Mediator conformations, thereby affecting transcription initiation/activation. We argue that Mediator is formed by highly disordered proteins with large densely packed interfaces that make effic... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5225807 Sun, 18 Sep 2011 01:41:59 +0100 5225807 http://www.medworm.com/index.php?rid=5225806&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21916847%26dopt%3DAbstract Authors: Hansen BG, Sun XE, Genee HJ, Kaas CS, Nielsen JB, Mortensen UH, Frisvad JC, Hedstrom L Abstract Mycophenolic acid (MPA) is an immunosuppressive drug produced by several fungi in Penicillium subgenus Penicillium. This toxic metabolite is an inhibitor of IMP dehydrogenase (IMPDH). The MPA biosynthetic cluster of P. brevicompactum contains a gene encoding a B-type IMPDH, IMPDH-B, which confers MPA-resistance. Surprisingly, all members of subgenus Penicillium contain genes encoding IMPDHs of both the A and B type, regardless of their ability to produce MPA. Duplication of the IMPDH gene occurred prior to and independent of the acquisition of the MPA biosynthetic cluster. Both P. brevicompactum IMPDHs are MPA-resistant while the IMPDHs from a nonproducer are MPA-sensitive. Resi... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5225806 Thu, 15 Sep 2011 04:00:00 +0100 5225806 http://www.medworm.com/index.php?rid=5225805&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21916849%26dopt%3DAbstract Authors: Wang X, Wang L, Wang X, Sun F, Wang CC Abstract Prx4 (peroxiredoxin 4) is the only peroxiredoxin located in the ER (endoplasmic reticulum) and a proposed scavenger for H2O2. In this work we presented crystal structures of human Prx4 in three different redox forms and characterized the reaction features of Prx4 with H2O2. Prx4 exhibits a toroid-shaped decamer constructed of five catalytic dimers. Structural analysis revealed conformational changes around helix α2 and the C-terminal reigon with a YF motif from the partner subunit, which are required for inter-chain disulfide formation between Cys87 and Cys208, a critical step of the catalysis. The structural explanation for the restricting role of the YF motif on the active site dynamics is provided in detail. Prx4 has a hi... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5225805 Thu, 15 Sep 2011 04:00:00 +0100 5225805 http://www.medworm.com/index.php?rid=5225804&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919885%26dopt%3DAbstract Authors: Hueso G, Aparicio-Sanchis R, Montesinos C, Lorenz S, Murguia JR, Serrano R Abstract Intracellular pH conditions many cellular systems but its mechanisms of regulation and perception are mostly unknown. We have identified two yeast genes important for tolerance to intracellular acidification caused by weak permeable acids. One corresponded to LEU2 and functions by removing the dependency of the leu2 mutant host strain on uptake of extracellular leucine. Leucine transport is inhibited by intracellular acidification and either leucine over-supplementation or over-expression of the transporter gene BAP2 improved acid growth. Another acid-tolerance gene is GCN2, encoding a protein kinase activated by uncharged tRNAs during amino acid starvation. Gcn2 phosphorylates eIF2α(Sui2)... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5225804 Thu, 15 Sep 2011 04:00:00 +0100 5225804 http://www.medworm.com/index.php?rid=5225803&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919886%26dopt%3DAbstract Authors: Knapp RT, Steiner A, Schmidt U, Hafner K, Holsboer F, Rein T Abstract Part of the cellular and physiological functions of BAG-1 has been ascribed to the ability of this hsp70 cochaperone to regulate steroid receptor activity. BAG-1 has been reported to inhibit the glucocorticoid receptor (GR), to stimulate the androgen receptor but to leave the activity of the mineralocorticoid receptor (MR) unchanged. Given the high homology between MR and GR, this disparity in the actions of BAG‑1 is surprising. Here we analyzed the effect of BAG-1 on the activity of the closely related progesterone receptor (PR). Similarly to GR, the transcriptional activity of PR is inhibited by the long and middle isoforms of BAG-1, BAG-1L and BAG-1M, but not by the short isoform BAG-1S. We found th... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5225803 Thu, 15 Sep 2011 04:00:00 +0100 5225803 http://www.medworm.com/index.php?rid=5225801&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21919888%26dopt%3DAbstract Authors: Wang X, Lu XA, Song X, Zhuo W, Jia L, Jiang Y, Luo Y Abstract Heat shock protein 90 (Hsp90) is one of the most important molecular chaperones in eukaryotes. Hsp90 facilitates the maturation, activation or degradation of its client proteins. It is now well accepted that both ATP binding and cochaperone association are involved in regulating the Hsp90 chaperone machinery. However, other factors such as post-translational modifications are getting increasingly noted to be involved in this process. Recent literatures have reported that phosphorylation of Hsp90 plays an unanticipated role in this process. Here, we systematically investigated the impact of phosphorylation of a single Threonine 90 (T90) residue of Hsp90α (pT90-Hsp90α) on its chaperone machinery. We demonstrate ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5225801 Thu, 15 Sep 2011 04:00:00 +0100 5225801 http://www.medworm.com/index.php?rid=5171229&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21867483%26dopt%3DAbstract Authors: O'Neill LA Abstract Macrophage activation is a key event in the inflammatory process, since these cells produce a range of pro-inflammatory molecules, including ROS (reactive oxygen species), prostaglandins, cytokines and nitric oxide. These factors promote inflammation by causing vasodilation and recruitment of neutrophils, monocytes and lymphocytes, which ultimately clear infection and repair damaged tissue. One of the most potent macrophage activators is the Gram-negative-derived bacterial cell wall component LPS (lipopolysaccharide). LPS is sensed by TLR4 (Toll-like receptor 4) and triggers highly complex signalling pathways that culminate in activation of transcription factors such as NF-κB (nuclear factor κB), which in turn increases transcription of genes encoding... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5171229 Mon, 29 Aug 2011 17:24:25 +0100 5171229 http://www.medworm.com/index.php?rid=5171228&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21867484%26dopt%3DAbstract Authors: Werner ER, Blau N, Thöny B Abstract BH4 (6R-L-erythro-5,6,7,8-tetrahydrobiopterin) is an essential cofactor of a set of enzymes that are of central metabolic importance, including four aromatic amino acid hydroxylases, alkylglycerol mono-oxygenase and three NOS (NO synthase) isoenzymes. Consequently, BH4 is present in probably every cell or tissue of higher organisms and plays a key role in a number of biological processes and pathological states associated with monoamine neurotransmitter formation, cardiovascular and endothelial dysfunction, the immune response and pain sensitivity. BH4 is formed de novo from GTP via a sequence of three enzymatic steps carried out by GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase. An alternative or sa... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5171228 Mon, 29 Aug 2011 17:24:18 +0100 5171228 http://www.medworm.com/index.php?rid=5171227&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21867485%26dopt%3DAbstract Authors: Friedman R Abstract Amyloid-related diseases are a group of illnesses in which an abnormal accumulation of proteins into fibrillar structures is evident. Results from a wide range of studies, ranging from identification of amyloid-β dimers in the brain to biophysical characterization of the interactions between amyloidogenic peptides and lipid membranes during fibril growth shed light on the initial events which take place during amyloid aggregation. Accounts of fibril disaggregation and formation of globular aggregates due to interactions with lipids or fatty acids further demonstrate the complexity of the aggregation process and the difficulty to treat amyloid-related diseases. There is an inherent difficulty in generalizing from studies of aggregation in vitro, but the... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5171227 Mon, 29 Aug 2011 17:24:10 +0100 5171227 http://www.medworm.com/index.php?rid=5138825&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21834794%26dopt%3DAbstract Authors: Birkholtz LM, Williams M, Niemand J, Louw AI, Persson L, Heby O New drugs are urgently needed for the treatment of tropical and subtropical parasitic diseases, such as African sleeping sickness, Chagas' disease, leishmaniasis and malaria. Enzymes in polyamine biosynthesis and thiol metabolism, as well as polyamine transporters, are potential drug targets within these organisms. In the present review, the current knowledge of unique properties of polyamine metabolism in these parasites is outlined. These properties include prozyme regulation of AdoMetDC (S-adenosylmethionine decarboxylase) activity in trypanosomatids, co-expression of ODC (ornithine decarboxylase) and AdoMetDC activities in a single protein in plasmodia, and formation of trypanothione, a unique compound linking... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5138825 Thu, 18 Aug 2011 10:31:45 +0100 5138825 http://www.medworm.com/index.php?rid=5138801&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21834795%26dopt%3DAbstract Authors: Scott CA, Kelsell DP Cx (connexin) proteins are components of gap junctions which are aqueous pores that allow intercellular exchange of ions and small molecules. Mutations in Cx genes are linked to a range of human disorders. In the present review we discuss mutations in β-Cx genes encoding Cx26, Cx30, Cx30.3 and Cx31 which lead to skin disease and deafness. Functional studies with Cx proteins have given insights into disease-associated mechanisms and non-gap junctional roles for Cx proteins. PMID: 21834795 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5138801 Thu, 18 Aug 2011 10:06:01 +0100 5138801 http://www.medworm.com/index.php?rid=5138786&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21838706%26dopt%3DAbstract Authors: Knudsen L, De Meyts P, Kiselyov VV More than 20 years after the description of the two insulin receptor (IR) isoforms, designed IR-A (lacking exon 11) and IR-B (with exon 11) nearly every functional aspect of the alternative splicing both in vitro and in vivo remains controversial. In particular, there is no consensus on the precise ligand binding properties of the isoforms. Increased affinity and dissociation kinetics have been reported for IR-A in comparison to IR-B, but the reverse results have also been reported. These are not trivial issues considering the reported possible increased mitogenic potency of IR-A, and the reported link between slower dissociation and increased mitogenesis. We have re-examined the ligand binding properties of the two isoforms using a novel rig... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5138786 Sun, 14 Aug 2011 23:00:00 +0100 5138786 http://www.medworm.com/index.php?rid=5138762&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21838707%26dopt%3DAbstract Authors: Schönherr C, Ruuth K, Yamazaki Y, Eriksson T, Christensen J, Palmer RH, Hallberg B Mutations in the kinase domain of Anaplastic Lymphoma Kinase (ALK) have recently been shown to be important for the progression of the childhood tumor neuroblastoma. Here we investigate six of the putative reported constitutively active ALK mutations, in positions G1128A, I1171N, F1174L, R1192P, F1245C and R1275Q. Our analyses were performed in cell culture based systems with both mouse and human ALK mutant variants and subsequently in a Drosophila melanogaster model system. Our investigation addressed the transforming potential of the putative gain-of-function ALK mutations as well as their signalling potential and the ability of two ATP-competitive inhibitors, Crizotinib (PF-02341066) and NVP... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5138762 Sun, 14 Aug 2011 23:00:00 +0100 5138762 http://www.medworm.com/index.php?rid=5138748&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843151%26dopt%3DAbstract Authors: Dell'orco D, Koch KW The early steps in vertebrate vision require fast interactions between rhodopsin (Rho) and transducin (Gt), which are classically described by a collisional coupling mechanism driven by the free diffusion of monomeric proteins on the disc membranes of rod and cone cells. Recent findings, however, point to a very low mobility for Rho and support a substantially different supramolecular organization. Moreover, Rho-Gt interactions seem to possibly occur even prior to light stimuli, which is also difficult to reconcile with the classical scenario. We investigated the kinetics of interaction between native Rho and Gt in different conditions by surface plasmon resonance and analysed the results in the general physiological context by employing a holistic systems... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5138748 Sun, 14 Aug 2011 23:00:00 +0100 5138748 http://www.medworm.com/index.php?rid=5088600&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21793802%26dopt%3DAbstract Authors: Brown AJ In humans, there are 48 members of the superfamily of nuclear receptors. These ligand-activated transcription factors help to integrate our growth, reproduction and metabolism via environmental, nutritional and intrinsic cues. It is therefore not surprising that nuclear receptors are commonly used as drug targets. However, perhaps in the rush to discover new drugs that target these receptors, we sometimes lose sight of their 'real' physiological ligands. In this issue of the Biochemical Journal Goto et al. present evidence that the isoprenoid FPP (farnesyl pyrophosphate) may be a bona fide ligand for the master controller of adipocyte differentiation PPARγ (peroxisome-proliferator-activated receptor γ). This work has wide-ranging implications not only for obesity an... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5088600 Wed, 03 Aug 2011 17:00:51 +0100 5088600 http://www.medworm.com/index.php?rid=5088599&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21793803%26dopt%3DAbstract Authors: Bermejo C, Ewald JC, Lanquar V, Jones AM, Frommer WB Over the past decade, we have learned that cellular processes, including signalling and metabolism, are highly compartmentalized, and that relevant changes in metabolic state can occur at sub-second timescales. Moreover, we have learned that individual cells in populations, or as part of a tissue, exist in different states. If we want to understand metabolic processes and signalling better, it will be necessary to measure biochemical and biophysical responses of individual cells with high temporal and spatial resolution. Fluorescence imaging has revolutionized all aspects of biology since it has the potential to provide information on the cellular and subcellular distribution of ions and metabolites with sub-second time reso... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5088599 Wed, 03 Aug 2011 17:00:44 +0100 5088599 http://www.medworm.com/index.php?rid=5088598&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21793804%26dopt%3DAbstract Authors: Hirai H, Karian P, Kikyo N LIF (leukaemia inhibitory factor) is a key cytokine for maintaining self-renewal and pluripotency of mESCs (mouse embryonic stem cells). Upon binding to the LIF receptor, LIF activates three major intracellular signalling pathways: the JAK (Janus kinase)/STAT3 (signal transducer and activator of transcription 3), PI3K (phosphoinositide 3-kinase)/AKT and SHP2 [SH2 (Src homology 2) domain-containing tyrosine phosphatase 2]/MAPK (mitogen-activated protein kinase) pathways. These pathways converge to orchestrate the gene expression pattern specific to mESCs. Among the many signalling events downstream of the LIF receptor, activation and DNA binding of the transcription factor STAT3 plays a central role in transducing LIF's functions. The fundamental role... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5088598 Wed, 03 Aug 2011 17:00:38 +0100 5088598 http://www.medworm.com/index.php?rid=5088596&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21806544%26dopt%3DAbstract Authors: Salameh MA, Soares AS, Hockla A, Radisky DC, Radisky ES PRSS3/mesotrypsin is an atypical isoform of trypsin, the upregulation of which has been implicated in promoting tumor progression. Mesotrypsin inhibitors could potentially provide valuable research tools and novel therapeutics, but small molecule trypsin inhibitors have low affinity and little selectivity, while protein trypsin inhibitors bind poorly and are rapidly degraded by mesotrypsin. Here, we use mutagenesis of a mesotrypsin substrate, the Kunitz domain of the amyloid precursor protein (APPI), and of a poor mesotrypsin inhibitor, bovine pancreatic trypsin inhibitor (BPTI), to dissect mesotrypsin specificity at the key P2' position. We find that bulky and charged residues strongly disfavor binding, while acidic resi... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5088596 Mon, 01 Aug 2011 23:00:00 +0100 5088596 http://www.medworm.com/index.php?rid=5088597&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21806543%26dopt%3DAbstract Authors: Cameron AJ, Linch MD, Saurin AT, Escribano C, Parker PJ The protein kinase Target of rapamycin (TOR) is a key regulator of cell growth and metabolism with significant clinical relevance. TOR signals through two distinct multi-protein complexes, mTORC1 and mTORC2, the subunits of which appear to define the operational pathways. Rapamycin selectively targets mTORC1 function and the emergence of specific ATP competitive kinase inhibitors has enabled assessment of dual mTORC1 and mTORC2 blockade. Little is known however concerning the molecular action of mTORC2 components or the relative importance of targeting this pathway. Here we identify the mTORC2 subunit Sin1 as a direct binding partner of the PKCε kinase domain and map the interaction to the central, highly conserved regio... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5088597 Sun, 31 Jul 2011 23:00:00 +0100 5088597 http://www.medworm.com/index.php?rid=5038820&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21749321%26dopt%3DAbstract Authors: Said HM Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtai... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5038820 Wed, 20 Jul 2011 06:01:08 +0100 5038820 http://www.medworm.com/index.php?rid=5038819&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21749322%26dopt%3DAbstract Authors: Igamberdiev AU, Kleczkowski LA Stress conditions (e.g. anoxia) frequently result in a decrease of [ATP] and in an increase of [ADP] and [AMP], with a concomitant increase of [Mg2+] and other cations, e.g. Ca2+. The elevation of [Mg2+] is linked to the shift in the apparent equilibrium of adenylate kinase. As a result, enzymes that use Mg2+ as a cofactor are activated, Ca2+ activates calcium-dependent signalling pathways, and PPi can serve as an alternative energy source in its active form of MgPPi or Mg2PPi. Under anoxic conditions in plants, an important source of PPi may come as a result of combined reactions of PK (pyruvate kinase) and PPDK (pyruvate, phosphate dikinase). The PPi formed in the PPDK/PK cycle ignites glycolysis in conditions of low [ATP] by involving PPi-depe... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5038819 Wed, 20 Jul 2011 06:01:02 +0100 5038819 http://www.medworm.com/index.php?rid=5038818&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21749323%26dopt%3DAbstract Authors: Cater MA, Haupt Y PMID: 21749323 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5038818 Wed, 20 Jul 2011 06:00:58 +0100 5038818 http://www.medworm.com/index.php?rid=5038817&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21749324%26dopt%3DAbstract Authors: Brand MD, Nicholls DG PMID: 21749324 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5038817 Wed, 20 Jul 2011 06:00:46 +0100 5038817 http://www.medworm.com/index.php?rid=5038816&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21749325%26dopt%3DAbstract Authors: Hao Y, Perkinton MS, Chan WW, Chan HY, Miller CC, Lau KF PMID: 21749325 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5038816 Wed, 20 Jul 2011 06:00:33 +0100 5038816 http://www.medworm.com/index.php?rid=5038821&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21745186%26dopt%3DAbstract Authors: Murphy G, Poole AR This 'Biochemical Journal Classic' paper reflects a remarkable example of how a biochemist and a biologist came together in the 1920s to solve a biological problem that set the stage for bone and cartilage research today, and demonstrates the great strengths and importance of interdisciplinary collaborations. PMID: 21745186 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5038821 Wed, 20 Jul 2011 06:00:03 +0100 5038821 http://www.medworm.com/index.php?rid=5038815&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21756249%26dopt%3DAbstract Authors: Benjamin S, Weidberg H, Rapaport D, Pekar O, Nudelman M, Segal D, Hirschberg K, Katzav S, Ehrlich M, Horowitz M EHDs, EH domain containing proteins, participate in different stages of endocytosis. EHD2 is a plasma membrane associated, EHD which regulates trafficking from the plasma membrane [1]and recycling [2]. EHD2 has a role in nucleotide dependent membrane remodeling and its ATP binding domain is involved in dimerization, which creates a membrane binding region. Nucleotide binding is important for association of EHD2 with the plasma membrane, since a nucleotide free mutant (EHD2 T72A) failed to do so [3]. To elucidate the possible function of EHD2 during endocytic trafficking we attempted to unravel proteins that interact with EHD2, using the yeast two-hybrid system. A nov... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5038815 Thu, 14 Jul 2011 23:00:00 +0100 5038815 http://www.medworm.com/index.php?rid=5038814&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762109%26dopt%3DAbstract We report that Group IVA cytosolic phospholipase A2 (PLA2G4A) is important in the development and function of rodent testes. Interstitial cells of rat testes had high PLA2 activity that was very sensitive to the PLA2G4A-preferential inhibitor AACOCF3. PLA2G4A protein was expressed primarily in interstitial cells of wild-type mouse testes throughout maturation. While Pla2g4a knockout (Pla2g4a-/-) male mice are fertile, their sexual maturation was delayed as indicated by cauda epididymal sperm count and seminal vesicle development. Delayed function of Pla2g4a-/- testes was associated with histological abnormalities including disorganized architecture, swollen appearance, and fewer interstitial cells. Basal secretion of testosterone was significantly attenuated and steroidogenic response to h... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=5038814 Thu, 14 Jul 2011 23:00:00 +0100 5038814 http://www.medworm.com/index.php?rid=4994678&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21711245%26dopt%3DAbstract Authors: Hirst J The prokaryotic and eukaryotic homologues of complex I (proton-pumping NADH:quinone oxidoreductase) perform the same function in energy transduction, but the eukaryotic enzymes are twice as big as their prokaryotic cousins, and comprise three times as many subunits. Fourteen core subunits are conserved in all complexes I, and are sufficient for catalysis - so why are the eukaryotic enzymes embellished by so many supernumerary or accessory subunits? In this issue of the Biochemical Journal, Angerer et al. have provided new evidence to suggest that the supernumerary subunits are important for enzyme stability. This commentary aims to put this suggestion into context. PMID: 21711245 [PubMed - in process] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4994678 Mon, 04 Jul 2011 16:15:20 +0100 4994678 http://www.medworm.com/index.php?rid=4994677&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21711246%26dopt%3DAbstract Authors: Koch S, Tugues S, Li X, Gualandi L, Claesson-Welsh L VEGFs (vascular endothelial growth factors) control vascular development during embryogenesis and the function of blood vessels and lymphatic vessels in the adult. There are five related mammalian ligands, which act through three receptor tyrosine kinases. Signalling is modulated through neuropilins, which act as VEGF co-receptors. Heparan sulfate and integrins are also important modulators of VEGF signalling. Therapeutic agents that interfere with VEGF signalling have been developed with the aim of decreasing angiogenesis in diseases that involve tissue growth and inflammation, such as cancer. The present review will outline the current understanding and consequent biology of VEGF receptor signalling. PMID: 21711246 [Pu... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4994677 Mon, 04 Jul 2011 16:15:16 +0100 4994677 http://www.medworm.com/index.php?rid=4994676&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21711247%26dopt%3DAbstract Authors: Fredman G, Serhan CN Inflammation when unchecked is associated with many prevalent disorders such as the classic inflammatory diseases arthritis and periodontal disease, as well as the more recent additions that include diabetes and cardiovascular maladies. Hence mechanisms to curtail the inflammatory response and promote catabasis are of immense interest. In recent years, evidence has prompted a paradigm shift whereby the resolution of acute inflammation is a biochemically active process regulated in part by endogenous PUFA (polyunsaturated fatty acid)-derived autacoids. Among these are a novel genus of SPMs (specialized proresolving mediators) that comprise novel families of mediators including lipoxins, resolvins, protectins and maresins. SPMs have distinct structures and a... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4994676 Mon, 04 Jul 2011 16:15:11 +0100 4994676 http://www.medworm.com/index.php?rid=4994675&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21711248%26dopt%3DAbstract Authors: Wesche J, Haglund K, Haugsten EM FGFs (fibroblast growth factors) and their receptors (FGFRs) play essential roles in tightly regulating cell proliferation, survival, migration and differentiation during development and adult life. Deregulation of FGFR signalling, on the other hand, has been associated with many developmental syndromes, and with human cancer. In cancer, FGFRs have been found to become overactivated by several mechanisms, including gene amplification, chromosomal translocation and mutations. FGFR alterations are detected in a variety of human cancers, such as breast, bladder, prostate, endometrial and lung cancers, as well as haematological malignancies. Accumulating evidence indicates that FGFs and FGFRs may act in an oncogenic fashion to promote multiple step... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4994675 Mon, 04 Jul 2011 16:15:07 +0100 4994675 http://www.medworm.com/index.php?rid=4945899&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21668411%26dopt%3DAbstract Authors: Barbolina MV, Burkhalter RJ, Stack MS Wnt signalling pathways have been shown to play key roles in both normal development and tumorigenesis. Progression of many human cancers is associated with defined mutations in Wnt pathway components that result in dysregulated β-catenin-mediated gene transcription. Although Wnt pathway mutations are rare in epithelial ovarian cancer (with the exception of the endometrioid histotype), accumulating evidence supports a role for Wnt signalling in ovarian tumorigenesis in the absence of genetic mutations. The present review summarizes evidence in support of activated Wnt signalling in ovarian tumours and discusses alternative mechanisms for Wnt pathway activation in the ovarian tumour microenvironment. PMID: 21668411 [PubMed - in process... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4945899 Mon, 20 Jun 2011 11:30:31 +0100 4945899 http://www.medworm.com/index.php?rid=4945898&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21668412%26dopt%3DAbstract Authors: Neto H, Collins LL, Gould GW All cells complete cell division by the process of cytokinesis. At the end of mitosis, eukaryotic cells accurately mark the site of division between the replicated genetic material and assemble a contractile ring comprised of myosin II, actin filaments and other proteins, which is attached to the plasma membrane. The myosin-actin interaction drives constriction of the contractile ring, forming a cleavage furrow (the so-called 'purse-string' model of cytokinesis). After furrowing is completed, the cells remain attached by a thin cytoplasmic bridge, filled with two anti-parallel arrays of microtubules with their plus-ends interdigitating in the midbody region. The cell then assembles the abscission machinery required for cleavage of the intercellular... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4945898 Mon, 20 Jun 2011 11:30:26 +0100 4945898 http://www.medworm.com/index.php?rid=4945897&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21668413%26dopt%3DAbstract Authors: Jono H, Anno T, Motoyama K, Misumi Y, Tasaki M, Oshima T, Mori Y, Mizuguchi M, Ueda M, Shono M, Obayashi K, Arima H, Ando Y TTR (transthyretin), a β-sheet-rich protein, is the precursor protein of familial amyloidotic polyneuropathy and senile systemic amyloidosis. Although it has been widely accepted that protein misfolding of the monomeric form of TTR is a rate-limiting step for amyloid formation, no effective therapy targeting this misfolding step is available. In the present study, we focused on CyDs (cyclodextrins), cyclic oligosaccharides composed of glucose units, and reported the inhibitory effect of CyDs on TTR amyloid formation. Of various branched β-CyDs, GUG-β-CyD [6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-β-CyD] showed potent inhibition of TTR amyloid formation.... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4945897 Mon, 20 Jun 2011 11:30:23 +0100 4945897 http://www.medworm.com/index.php?rid=4945894&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679160%26dopt%3DAbstract Authors: Parra E, Moleiro LH, Lopez-Montero I, Cruz A, Monroy F, Perez-Gil J Proteins SP-B and SP-C are essential to promote formation of surface active films at the respiratory interface, but their mechanism of action is still under investigation. We have analyzed the effect of the proteins on the accessibility of native, quasi-native and model surfactant membranes to incorporation of fluorescent probes Nile Red (permeable) and FM®1-43 (impermeable) to membranes. We have also analyzed the effect of single or combined proteins on membrane permeation by the soluble fluorescent dye calcein. Fluorescence of FM 1-43 was always higher in membranes containing SP-B and/or SP-C than in protein-depleted membranes, in contrast to Nile Red, very similar in all the materials tested. SP-B and SP-C... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4945894 Wed, 15 Jun 2011 23:00:00 +0100 4945894 http://www.medworm.com/index.php?rid=4945893&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21679161%26dopt%3DAbstract Authors: Polimeni M, Voena C, Kopecka J, Riganti C, Pescarmona G, Bosia A, Ghigo D How anti-neoplastic agents induce multidrug resistance (MDR) in cancer cells and the role of glutathione (GSH) in the activation of pumps such as the multidrug resistance-associated proteins (MRPs) are still open questions. In this paper we illustrate that a doxorubicin-resistant human colon cancer cell line (HT29-DX), exhibiting decreased doxorubicin accumulation and increased intracellular GSH content and MRP1 and MRP2 expression in comparison to doxorubicin-sensitive HT29 cells, shows increased activity of the pentose phosphate pathway (PPP) and of glucose 6-phosphate dehydrogenase (G6PD). We observed the onset of MDR in HT29 cells overexpressing G6PD, accompanied by an increase of GSH; the G6PD inhib... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4945893 Wed, 15 Jun 2011 23:00:00 +0100 4945893 http://www.medworm.com/index.php?rid=4945896&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21675959%26dopt%3DAbstract Authors: Srivastav RK, Schwede S, Klaus M, Schwermann J, Gaestel M, Niedenthal R Protein-protein interactions are essential for almost all cellular processes and, hence, understanding these processes mainly depends on the identification and characterization of the relevant protein-protein interactions. Here, we introduce the concept of Trans-SUMOylation (TRS), a new method developed to identify and verify protein-protein interactions in mammalian cells in vivo. TRS utilizes Ubc9 fusion proteins that trans-SUMOylate coexpressed interacting proteins. Using TRS, we analysed interactions of 65 protein pairs coexpressed in HEK293 cells. We identified seven new and confirmed sixteen known protein interactions, which were determined via endogenous SUMOylation sites of the binding partners or ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4945896 Tue, 14 Jun 2011 23:00:00 +0100 4945896 http://www.medworm.com/index.php?rid=4945895&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21675960%26dopt%3DAbstract Authors: Yan M, Li J, Sha B Sil1 functions as a nucleotide exchange factor (NEF) for Bip in eukaryotic cells. In order to understand how Sil1 functions as a NEF, we analyzed the crystal structure of the yeast Bip-Sil1 complex at a resolution of 2.3Å. In the complex, the Sil1 molecule acts as a "molecular clamp" which binds to the IIb lobe of the Bip ATPase domain. Sil1 binding causes lobe IIb to rotate ~13.5° away from the ADP-binding pocket and lobe Ib to rotate in the opposite direction for ~3.7°. These conformational changes in Bip open up the nucleotide-binding pocket in the ATPase domain and simultaneously disrupt the hydrogen bonds between Bip and bound ADP, thus providing a mechanism for ADP release. We also demonstrate that Sil1 mutations that disrupt binding to the Bip ATPa... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4945895 Tue, 14 Jun 2011 23:00:00 +0100 4945895 http://www.medworm.com/index.php?rid=4897422&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21615332%26dopt%3DAbstract Authors: Anand-Ivell R, Ivell R Spermatozoa represent a highly specialized cell type, with a minimalist structure designed to fulfil a single principal function: the transport of an intact single-copy haploid genome to the site of fertilization in the oviduct, and consequent zygote formation. They have lost most of their original cytoplasm, and remaining organelles are extremely modified. One result of this is that biochemical dynamics are restricted by a lack of cytoplasmic diffusion and a dramatic compartmentalization, with an increased emphasis on the physicochemical modulation of membranes. This is also reflected in a truncated apoptotic pathway, described in this issue of the Biochemical Journal in an article by Koppers et al., which leads to a so-called 'silent response' in the f... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4897422 Mon, 06 Jun 2011 04:31:15 +0100 4897422 http://www.medworm.com/index.php?rid=4897421&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21615333%26dopt%3DAbstract Authors: Davies AH, Roberts AK, Shone CC, Acharya KR Clostridium difficile, a highly infectious bacterium, is the leading cause of antibiotic-associated pseudomembranous colitis. In 2009, the number of death certificates mentioning C. difficile infection in the U.K. was estimated at 3933 with 44% of certificates recording infection as the underlying cause of death. A number of virulence factors facilitate its pathogenicity, among which are two potent exotoxins; Toxins A and B. Both are large monoglucosyltransferases that catalyse the glucosylation, and hence inactivation, of Rho-GTPases (small regulatory proteins of the eukaryote actin cell cytoskeleton), leading to disorganization of the cytoskeleton and cell death. The roles of Toxins A and B in the context of C. difficile infection ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4897421 Mon, 06 Jun 2011 04:31:05 +0100 4897421 http://www.medworm.com/index.php?rid=4897420&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21615334%26dopt%3DAbstract Authors: Nam EA, Cortez D Preservation of genome integrity via the DNA-damage response is critical to prevent disease. ATR (ataxia telangiectasia mutated- and Rad3-related) is essential for life and functions as a master regulator of the DNA-damage response, especially during DNA replication. ATR controls and co-ordinates DNA replication origin firing, replication fork stability, cell cycle checkpoints and DNA repair. Since its identification 15 years ago, a model of ATR activation and signalling has emerged that involves localization to sites of DNA damage and activation through protein-protein interactions. Recent research has added an increasingly detailed understanding of the canonical ATR pathway, and an appreciation that the canonical model does not fully capture the complexity ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4897420 Mon, 06 Jun 2011 04:30:55 +0100 4897420 http://www.medworm.com/index.php?rid=4897416&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21635223%26dopt%3DAbstract Authors: Botkjaer KA, Fogh S, Bekes EC, Zhou C, Blouse GE, Jensen JM, Mortensen KK, Huang M, Deryugina E, Quigley JP, Declerck PJ, Andreasen PA Tight regulation of serine proteases is essential for their physiological functions and unbalanced states of protease activity have been implicated in a variety of human diseases. One key example is the presence of urokinase-type plasminogen activator (uPA) in different human cancer types, with high levels correlating with a poor prognosis. This observation has stimulated efforts into finding new principles for intervening with uPA's activity. We have now characterised the so-called autolysis loop in the catalytic domain of uPA as a potential inhibitory target. This loop was found to harbour the epitopes for three conformation-specific monoclon... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4897416 Wed, 01 Jun 2011 23:00:00 +0100 4897416 http://www.medworm.com/index.php?rid=4897415&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21635224%26dopt%3DAbstract Authors: Geistrikh I, Visochek L, Klein R, Miller L, Mittelman L, Shainberg A, Cohen-Armon M The nuclear protein PARP-1 is activated in cardiomyocytes exposed to hypoxia causing DNA breaks. Unlike this stress-induced PARP-1 activation, our results provide evidence for Ca2+ induced PARP-1 activation in contracting newborns' cardiomyocytes treated with growth factors and hormons that increased their contraction rate, induced intracellular Ca2+ mobilization and its rhythmical and transient translocation into the nucleus. Furthermore, activated PARP-1 up-regulated the activity of phosphorylated ERK in the nucleus, promoting expression of Elk1 target gene, c-fos. Up-regulation of transcription factor c-Fos\GATA-4 promoted ANF expression. Given that expression of atrial naturetic factor (ANF... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4897415 Wed, 01 Jun 2011 23:00:00 +0100 4897415 http://www.medworm.com/index.php?rid=4897419&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21631430%26dopt%3DAbstract Authors: Schwarzlander M, Logan DC, Fricker MD, Sweetlove L The properties of a circularly-permuted YFP (cpYFP) reported to act as a superoxide sensor have been re-examined in Arabidopsis mitochondria. We find that the probe has high pH-sensitivity and that dynamics in the cpYFP signal disappeared when matrix pH was clamped by nigericin. In contrast, genetic and pharmacological manipulation of matrix superoxide had no detectable effect on the cpYFP signal. These findings question the existence of superoxide 'flashes' in mitochondria. PMID: 21631430 [PubMed - as supplied by publisher] (Source: The Biochemical Journal) The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4897419 Tue, 31 May 2011 23:00:00 +0100 4897419 http://www.medworm.com/index.php?rid=4897418&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21631431%26dopt%3DAbstract Authors: Lambert QT, Pradhan A, Roll JD, Reuther GW Cytokines and their receptors regulate hematopoiesis by controlling cellular growth, survival, and differentiation. Thus, it is not surprising that mutations of cytokine receptors contribute to the formation of hematopoietic disorders including cancer. We recently identified transforming properties of the ligand-binding component of the receptor for interleukin-27 (IL27R). While wildtype IL27R exhibits transforming properties in hematopoietic cells, in this study we set out to determine if the transforming activity of IL27R could be enhanced by mutation. We identified three mutations of IL27R that enhance its transforming activity. One of these mutations is a phenylalanine to cysteine mutation at residue 523 (F523C) in the transmembra... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4897418 Tue, 31 May 2011 23:00:00 +0100 4897418 http://www.medworm.com/index.php?rid=4897417&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21631432%26dopt%3DAbstract Authors: Dixon DP, Sellars JD, Edwards R The plant-specific phi class of glutathione transferases (GSTFs) are often highly stress-inducible and expressed in a tissue-specific manner, suggestive of them having important protective roles. To date, these functions remain largely unknown, although activities associated with the binding and transport of reactive metabolites have been proposed. Using a sensitive and selective binding screen, we have probed the Arabidopsis thaliana GSTFs for natural product ligands from bacteria and plants. Uniquely, when over-expressed in bacteria, family members GSTF2 and GSTF3 bound a series of heterocyclic compounds including lumichrome, harmane, norharmane and indole-3-aldehyde. When screened against total metabolite extracts from A. thaliana, GSTF2 also... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4897417 Tue, 31 May 2011 23:00:00 +0100 4897417 http://www.medworm.com/index.php?rid=4851093&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568939%26dopt%3DAbstract Authors: Aronsson H, Jarvis P Pre-protein import into chloroplasts is facilitated by multiprotein translocon complexes in the envelope membranes. Major components of the TOC (translocon at the outer envelope membrane of chloroplasts) complex are the receptor proteins Toc33 and Toc159. These two receptors are related GTPases, and they are predicted to engage in homodimerization and/or heterodimerization. Although such dimerization has been studied extensively, its exact function in vivo remains elusive. In this issue of the Biochemical Journal, Oreb et al. present evidence that homodimerization of Toc33 prevents nucleotide exchange, thereby locking the receptor in the GDP-loaded state and preventing further activity. Pre-protein arrival is proposed to release this lock, through disrupti... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851093 Mon, 23 May 2011 03:31:22 +0100 4851093 http://www.medworm.com/index.php?rid=4851092&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568940%26dopt%3DAbstract Authors: Bröer S, Palacín M Amino acids are essential building blocks of all mammalian cells. In addition to their role in protein synthesis, amino acids play an important role as energy fuels, precursors for a variety of metabolites and as signalling molecules. Disorders associated with the malfunction of amino acid transporters reflect the variety of roles that they fulfil in human physiology. Mutations of brain amino acid transporters affect neuronal excitability. Mutations of renal and intestinal amino acid transporters affect whole-body homoeostasis, resulting in malabsorption and renal problems. Amino acid transporters that are integral parts of metabolic pathways reduce the function of these pathways. Finally, amino acid uptake is essential for cell growth, thereby explaining ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851092 Mon, 23 May 2011 03:31:18 +0100 4851092 http://www.medworm.com/index.php?rid=4851091&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568941%26dopt%3DAbstract Authors: Genevet A, Tapon N The establishment and maintenance of apico-basal cell polarity is a pre-requisite for the formation of a functioning epithelial tissue. Many lines of evidence suggest that cell polarity perturbations favour cancer formation, even though the mechanistic basis for this link remains unclear. Studies in Drosophila have uncovered complex interactions between the conserved Hpo (Hippo) tumour suppressor pathway and apico-basal polarity determinants. The Hpo pathway is a crucial growth regulatory network whose inactivation in Drosophila epithelial tissues induces massive overproliferation. Its core consists of a phosphorylation cascade (comprising the kinases Hpo and Warts) that mediates the inactivation of the pro-growth transcriptional co-activator Yki [Yorkie; YA... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851091 Mon, 23 May 2011 03:31:14 +0100 4851091 http://www.medworm.com/index.php?rid=4851090&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568942%26dopt%3DAbstract Authors: Lur G, Sherwood MW, Ebisui E, Haynes L, Feske S, Sutton R, Burgoyne RD, Mikoshiba K, Petersen OH, Tepikin AV Orai1 proteins have been recently identified as subunits of SOCE (store-operated Ca2+ entry) channels. In primary isolated PACs (pancreatic acinar cells), Orai1 showed remarkable co-localization and co-immunoprecipitation with all three subtypes of IP3Rs (InsP3 receptors). The co-localization between Orai1 and IP3Rs was restricted to the apical part of PACs. Neither co-localization nor co-immunoprecipitation was affected by Ca2+ store depletion. Importantly we also characterized Orai1 in basal and lateral membranes of PACs. The basal and lateral membranes of PACs have been shown previously to accumulate STIM1 (stromal interaction molecule 1) puncta as a result of Ca2+ s... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851090 Mon, 23 May 2011 03:31:10 +0100 4851090 http://www.medworm.com/index.php?rid=4851077&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21595632%26dopt%3DAbstract Authors: Liang HP, Brophy TM, Hogg PJ Tissue Factor (TF) is a trans-membrane cofactor that initiates blood coagulation in mammals by binding factor VIIa to activate factors X and IX. The cofactor can reside in a cryptic configuration on primary cells and de-encryption may involve a redox change in the C-terminal domain Cys186-Cys209 disulfide bond. The redox potential of the bond, the spacing of the reduced cysteine thiols and their oxidation by TF activators was investigated to test the involvement of the dithiol/disulfide in TF activation. A standard redox potential of -278 mV was determined for the Cys186-Cys209 disulfide of recombinant soluble TF. Notably, ablating the N-terminal domain Cys49-Cys57 disulfide markedly increased the redox potential of the Cys186-Cys209 bond, suggesti... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851077 Thu, 19 May 2011 23:00:00 +0100 4851077 http://www.medworm.com/index.php?rid=4851080&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592087%26dopt%3DAbstract Authors: Véret J, Coant N, Berdyshev E, Skobeleva A, Therville N, Bailbé D, Gorshkova I, Natarajan V, Portha B, Le Stunff H Pancreatic β-cell apoptosis induced by palmitate requires high glucose concentrations. Ceramides have been suggested to be important mediators of gluco-lipotoxicity-induced β-cell apoptosis. In INS-1 β-cells, 0.4 mM palmitate with 5 mM glucose increased the levels of dihydrosphingosine and dihydroceramides, two lipid intermediates in the de novo biosynthesis of ceramides, without inducing apoptosis. Increasing glucose concentrations to 30 mM amplified palmitate-induced accumulation of dihydrosphingosine and the formation of (dihydro)-ceramides. Of note, gluco-lipotoxicity specifically induced the formation of 18:0, 22:0 and 24:1 (dihydro)-ceramide molecular s... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851080 Wed, 18 May 2011 23:00:00 +0100 4851080 http://www.medworm.com/index.php?rid=4851079&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592088%26dopt%3DAbstract Authors: Thaa B, Levental I, Herrmann A, Veit M The influenza virus transmembrane protein M2 is a proton channel, but also plays a role in the scission of nascent virus particles from the plasma membrane. An amphiphilic helix in the cytoplasmic tail (CT) of M2 is supposed to insert into the lipid bilayer thereby inducing curvature. Palmitoylation of the helix and binding to cholesterol via putative CRAC (cholesterol recognition/interaction amino acid consensus) motifs are believed to target M2 to the edge of rafts, the viral budding site. We tested preconditions of this model, i.e. that the CT interacts with membranes and that acylation and cholesterol binding affect targeting of M2. M2-CT, purified as a glutathione-S-transferase fusion protein, associated with [³H]-photocholesterol a... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851079 Wed, 18 May 2011 23:00:00 +0100 4851079 http://www.medworm.com/index.php?rid=4851078&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592089%26dopt%3DAbstract Authors: Jeon TI, Seo YK, Osborne TF Bitter taste-sensing receptors (T2Rs) are expressed in the oral cavity to prevent ingestion of dietary toxins through taste avoidance. They are also expressed in other cell-types including gut enteroendocrine cells where their physiological role is enigmatic. Previously, we proposed T2R dependent cholecystokinin (CCK) secretion from enteroendocrine cells limits absorption of dietary toxins but an active mechanism was lacking. Here we show T2R signaling activates ATP-binding cassette B1 (ABCB1) in intestinal cells through a CCK signaling mechanism. Phenylthiocarbamide (PTC), an agonist for the T2R38 bitter receptor, increased ABCB1 expression in both intestinal cells and mouse intestine. PTC induction of ABCB1 was decreased by either T2R38 siRNA or t... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851078 Wed, 18 May 2011 23:00:00 +0100 4851078 http://www.medworm.com/index.php?rid=4851083&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21585338%26dopt%3DAbstract Authors: Couture JP, Blouin R DLK is a key regulator of development, cell differentiation and apoptosis. Interestingly, recent studies have shown that DLK expression is up-regulated in 3T3-L1 cells induced to differentiate into adipocytes and that DLK knockdown impairs the expression of peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis. Because the PPARγ agonist rosiglitazone was found to increase DLK expression in 3T3-L1 cells, we hypothesized that PPARγ is required for the transcriptional activation of the DLK gene. To test this notion, we first examined the effects of pharmacological inhibition or shRNA-mediated depletion of PPARγ on DLK accumulation in 3T3-L1 cells undergoing differentiation. Besides blocking adipocyte conversion of 3T3-L... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851083 Tue, 17 May 2011 23:00:00 +0100 4851083 http://www.medworm.com/index.php?rid=4851082&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21585340%26dopt%3DAbstract Authors: Kukushkin NV, Alonzi DS, Dwek RA, Butters TD During quality control in the endoplasmic reticulum (ER), nascent glycoproteins are deglucosylated by ER glucosidases I and II. In the post-ER compartments, glycoprotein endo-α-mannosidase provides an alternative route for deglucosylation. Previous evidence suggests that endomannosidase non-selectively deglucosylates glycoproteins escaping quality control in the endoplasmic reticulum, facilitating secretion of aberrantly folded as well as normal glycoproteins. Here, we employ free oligosaccharides (FOS) released from degrading glycoproteins as biomarkers of ERAD, allowing us to gain a global rather than single protein-centered view on ER-associated degradation. Glucosidase inhibition was used to discriminate between glucosidase- an... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851082 Tue, 17 May 2011 23:00:00 +0100 4851082 http://www.medworm.com/index.php?rid=4851081&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21585341%26dopt%3DAbstract In this study, we found that AKR1B10 protein is secreted from normal intestinal epithelium and cultured cancer cells, as detected by newly developed sandwich enzyme-linked immunosorbent assay and Western blot. AKR1B10's secretion was not affected by protein synthesis inhibitor cycloheximide and classical protein secretion pathway inhibitor brefeldin A, but stimulated by temperature, ATP, Ca2+ and Ca2+ carrier ionomycin, lysosomotropic NH4Cl, G-protein activator GTPγS, and G-protein coupling receptor fMLP. ADP-ribosylation factor inhibitor Exo-1 and phospholipase C inhibitor U73122 inhibited the secretion of AKR1B10. In cultured cells, AKR1B10 is present in lysosomes and secreted together with Cathepsin D, a lysosomal marker. In the intestine, AKR1B10 is specifically expressed in mature ep... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851081 Tue, 17 May 2011 23:00:00 +0100 4851081 http://www.medworm.com/index.php?rid=4851085&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21585336%26dopt%3DAbstract Authors: Grant K, Carey NM, Mendoza M, Schulze J, Pilon M, Pilon-Smits EA, Van Hoewyk D APR2 is the dominant adenosine 5'-phosphosulfate reductase in the model plant Arabidopsis thaliana, and converts activated sulfate to sulfite, a key reaction in the sulfate reduction pathway. To determine if APR2 has a role in selenium tolerance and metabolism, a mutant Arabidopsis line (apr2-1) was studied. apr2-1 plants had decreased selenate tolerance and photosynthetic efficiency. Sulfur metabolism was perturbed in apr2-1 plants grown on selenate, as observed by an increase in total sulfur and sulfate, and a two-fold decrease in glutathione concentration. The altered sulfur metabolism in apr2-1 grown on selenate did not reflect typical sulfate starvation, as cysteine and methionine levels were i... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851085 Mon, 16 May 2011 23:00:00 +0100 4851085 http://www.medworm.com/index.php?rid=4851084&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21585337%26dopt%3DAbstract Authors: Medici D, Potenta S, Kalluri R Endothelial-mesenchymal transition (EndMT) is a critical process of cardiac development and disease progression. However, little is know about the signaling mechanisms that cause endothelial cells to transform into mesenchymal cells. Here we show that transforming growth factor-beta2 (TGF-beta2) stimulates EndMT through Smad, MEK, PI3K, and p38 MAPK signaling pathways. Inhibitors of these pathways prevent TGF-beta2-induced EndMT. Furthermore, we show that all of these pathways are essential for increasing expression of the cell adhesion suppressing transcription factor Snail. Inhibition of Snail with siRNA prevents TGF-beta2-induced EndMT. However, over-expression of Snail is not sufficient to cause EndMT. Chemical inhibition of GSK-3beta allows ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851084 Mon, 16 May 2011 23:00:00 +0100 4851084 http://www.medworm.com/index.php?rid=4851089&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21574958%26dopt%3DAbstract Authors: Esposito G, Cevenini A, Cuomo A, De Falco F, Sabbatino D, Pane F, Ruoppolo M, Salvatore F AF4 belongs to a family of proteins implicated in childhood lymphoblastic leukaemia, FRAXE mental retardation and ataxia. AF4 is a transcriptional activator that is involved in transcriptional elongation. Although AF4 has been implicated in MLL-related leukaemogenesis, AF4-dependent physiological mechanisms are not clearly defined. Proteins that interact with AF4 may play important roles also in mediating oncogenesis, and are potential targets for novel therapies. Using a functional proteomic approach involving tandem mass spectrometry and bioinformatics, we identified 51 AF4-interacting proteins of various Gene Ontology Categories. About 60% participate in transcription regulatory mechan... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851089 Sun, 15 May 2011 23:00:00 +0100 4851089 http://www.medworm.com/index.php?rid=4851088&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21574959%26dopt%3DAbstract In this study, we found that ectopic expression of PLU1 enhanced the invasive potential of the weakly invasive cells dependent on its demethylase activity. PLU1 was shown to repress the expression of KAT5 gene through its histone H3K4 demethylation on the promoter. The regulation of KAT5 by PLU1 was suggested to be responsible for the PLU1-induced cell invasion. First, knockdown of KAT5 similarly increased the invasive potential of the cells. Second, knockdown of PLU1 in the highly invasive cancer cells increased KAT5 expression and reduced the invasive activity. Third, simultaneous knockdown of KAT5 partially relieved the suppression of cell invasion imposed by PLU1 knockdown. Finally, we found that CD82, which was transcriptionally regulated by KAT5, might be a candidate effector of cell... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851088 Sun, 15 May 2011 23:00:00 +0100 4851088 http://www.medworm.com/index.php?rid=4851087&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21574960%26dopt%3DAbstract Authors: Gallego-Sandin S, Alonso MT, Garcia-Sancho J Calcium homeostasis modulator 1 (CALHM1), a membrane protein with similarity to NMDA receptor channels that localizes in the plasma membrane and the endoplasmic reticulum (ER)of neurons, has been shown to generate a plasma membrane Ca2+ conductance and has been proposed to influence Alzheimer Disease risk. In the present study we have investigated the effects of CALHM1 on intracellular Ca2+ handling in HEK293T cells by using targeted aequorins for selective monitorization of Ca2+ transport by organelles. We find that CALHM1 increases Ca2+ leak of the ER and, more importantly, reduces ER Ca2+ uptake by decreasing both the transport capacity and the Ca2+ affinity of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). As a result, the... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851087 Sun, 15 May 2011 23:00:00 +0100 4851087 http://www.medworm.com/index.php?rid=4851086&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21574961%26dopt%3DAbstract Authors: Norville IH, O'Shea K, Sarkar-Tyson M, Zheng S, Titball RW, Varani G, Harmer NJ Macrophage infectivity potentiators (Mips) are a subset of immunophilins associated with virulence in a range of micro-organisms. These proteins possess prolyl-peptide isomerase activity and are inhibited by drugs including rapamycin and tacrolimus. We determined the structure of the Mip homologue (BpML1) from the human pathogen and biowarfare threat Burkholderia pseudomallei by nuclear magnetic resonance and X-ray crystallography. The crystal structure suggests that key catalytic residues in the BpML1 active site have unexpected conformational flexibility consistent with a role in catalysis. The structure further revealed BpML1 binding to a helical peptide, in a manner resembling the physiological... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4851086 Sun, 15 May 2011 23:00:00 +0100 4851086 http://www.medworm.com/index.php?rid=4797799&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21524274%26dopt%3DAbstract Authors: Ruigrok VJ, Levisson M, Eppink MH, Smidt H, van der Oost J Antibodies are the most successful affinity tools used today, in both fundamental and applied research (diagnostics, purification and therapeutics). Nonetheless, antibodies do have their limitations, including high production costs and low stability. Alternative affinity tools based on nucleic acids (aptamers), polypeptides (engineered binding proteins) and inorganic matrices (molecular imprinted polymers) have received considerable attention. A major advantage of these alternatives concerns the efficient (microbial) production and in vitro selection procedures. The latter approach allows for the high-throughput optimization of aptamers and engineered binding proteins, e.g. aiming at enhanced chemical and physical stab... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4797799 Sun, 08 May 2011 13:16:02 +0100 4797799 http://www.medworm.com/index.php?rid=4797798&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21524275%26dopt%3DAbstract Authors: O'Leary B, Park J, Plaxton WC PEPC [PEP (phosphoenolpyruvate) carboxylase] is a tightly controlled enzyme located at the core of plant C-metabolism that catalyses the irreversible β-carboxylation of PEP to form oxaloacetate and Pi. The critical role of PEPC in assimilating atmospheric CO2 during C4 and Crassulacean acid metabolism photosynthesis has been studied extensively. PEPC also fulfils a broad spectrum of non-photosynthetic functions, particularly the anaplerotic replenishment of tricarboxylic acid cycle intermediates consumed during biosynthesis and nitrogen assimilation. An impressive array of strategies has evolved to co-ordinate in vivo PEPC activity with cellular demands for C4-C6 carboxylic acids. To achieve its diverse roles and complex regulation, PEPC belongs ... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4797798 Sun, 08 May 2011 13:15:58 +0100 4797798 http://www.medworm.com/index.php?rid=4797790&cid=s_37584_60_f&fid=37584&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21545356%26dopt%3DAbstract Authors: Angerer H, Zwicker K, Wumaier Z, Sokolova L, Heide H, Steger M, Kaiser S, Nübel E, Brutschy B, Radermacher M, Brandt U, Zickermann V Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is a very large membrane protein complex with a central function in energy metabolism. Complex I from the aerobic yeast Yarrowia lipolytica comprises 14 central subunits that harbour the bioenergetic core functions and at least 28 accessory subunits. Despite progress in structure determination the position of individual accessory subunits in the enzyme complex remains largely unknown. Proteomic analysis of subcomplex I-delta revealed that it lacked eleven subunits including the central subunits ND1 and ND3 forming the interface between the peripheral and the membrane arm in bacterial compl... The Biochemical Journal journals http://www.medworm.com/rss/comments.php?id=4797790 Wed, 04 May 2011 23:00:00 +0100 4797790