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 'FEBS Letters' source. Mon, 06 Feb 2012 13:31:40 +0100 http://www.medworm.com/index.php?rid=5635150&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579312000403%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635150 Fri, 27 Jan 2012 18:32:03 +0100 5635150 http://www.medworm.com/index.php?rid=5635153&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579312000270%2Fabstract%3Frss%3Dyes Highlights: ► Human airway trypsin-like protease (HAT) cleaves proMSP at the activating site. ► MSP processed by HAT is biologically active. ► HAT silencing in bronchial epithelial cells reduces phosphorylation of MSP receptor.Abstract: Macrophage-stimulating protein (MSP) circulates as a proform protein and requires proteolytic processing for activation. Respiratory ciliated cells express the MSP receptor, recepteur d’origine nantais (RON), at the apical surface, which reportedly has an important role in ciliary function. Like RON, human airway trypsin-like protease (HAT) is also expressed at the apical surface of ciliated cells. Here we show that HAT cleaves proMSP at the physiological activation site, Arg483-Val484. MSP processed by HAT could induce chemotactic responses and mor... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635153 Thu, 12 Jan 2012 05:00:00 +0100 5635153 http://www.medworm.com/index.php?rid=5635164&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579312000208%2Fabstract%3Frss%3Dyes This study elucidates the N-acylation of the N-terminal serine in the CDA peptide chain. This reaction is referred to as lipoinitiation and is shown to be catalyzed by the dissected starter C domain found at the N-terminus of Cda-PSI. The recombinantly produced C domain specifically interacts with 2,3-epoxyhexanoyl-S-ACP and catalyzes the transfer of the fatty acid moiety onto the amino group of PCP-bound serine with high selectivity for both carrier protein bound substrates at the donor and acceptor site. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635164 Wed, 11 Jan 2012 05:00:00 +0100 5635164 http://www.medworm.com/index.php?rid=5635163&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931200018X%2Fabstract%3Frss%3Dyes We report that its mutation enhances co-localization of HA with a cis-Golgi marker and retards Golgi-localized processing, such as acquisition of Endo-H resistant carbohydrates and proteolytic cleavage. In contrast, trimerization of the molecule in the ER and transport to the apical membrane were not affected. The second signal for raft-targeting, S-acylation at cytoplasmic cysteines, did not retard HA transport. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635163 Wed, 11 Jan 2012 05:00:00 +0100 5635163 http://www.medworm.com/index.php?rid=5635162&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579312000178%2Fabstract%3Frss%3Dyes Highlights: ► Yeast as a model system for drug mechanism of action. ► Mechanism for anti-diabetic and anti-obesity agent sodium tungstate. ► Tungstate modulates yeast translational control (GCN) pathway. ► Tungstate inhibits GCN negative regulator Glc7p phosphatase. ► Tungstate as a putative therapy on GCN-related diseases.Abstract: Tungstate counteracts diabetes and obesity in animal models, but its molecular mechanisms remain elusive. Our Saccharomyces cerevisiae-based approach has found that tungstate alleviated the growth defect induced by nutrient stress and enhanced the activation of the GCN pathway. Tungstate relieved the sensitivity to starvation of a gcn2-507 yeast hypomorphic mutant, indicating that tungstate modulated the GCN pathway downstream of Gcn2p. Interestingly,... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635162 Wed, 11 Jan 2012 05:00:00 +0100 5635162 http://www.medworm.com/index.php?rid=5635161&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579312000154%2Fabstract%3Frss%3Dyes Highlights: ► We investigate the role of VapB in RANKL-induced osteoclast differentiation. ► Knock-down of VapB suppressed osteoclastogenesis. ► Over-expression of VapB accelerated RANKL-mediated osteoclast differentiation by induction of NFATc1. ► VapB regulates RANKL-mediated osteoclastogenesis via PLCγ2-Ca2+-NFAT signaling.Abstract: VapB has been shown to regulate calcium homeostasis in amyotrophic lateral sclerosis. Calcium signaling is also important in metabolic bone diseases, but the role of VapB in the generation of osteoclasts for bone resorption during osteoclastogenesis is not known. Therefore, we investigated the role of VapB in RANKL-induced osteoclast differentiation. Interestingly, VapB is induced during osteoclastogenesis, and regulates osteoclast differentiation b... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635161 Wed, 11 Jan 2012 05:00:00 +0100 5635161 http://www.medworm.com/index.php?rid=5635160&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311009161%2Fabstract%3Frss%3Dyes Highlights: ► Transcription factor CI changes its structure upon DNA-binding. ► Differential protein dynamics upon binding with different DNA sequences. ► Exploration of dynamical time scale associated with the protein–DNA interaction. ► Structural aspects of DNA-bound CI–CI co-operative interactions are investigated.Abstract: λ-Repressor–operator sites interaction, particularly OR1 and OR2, is a key component of the λ-genetic switch. FRET from the dansyl bound to the C-terminal domain of the protein, to the intercalated EtBr in the operator DNA indicates that the structure of the protein is more compact in the OR2 complex than in the OR1 complex. Fluorescence anisotropy reveals enhanced flexibility of the C-terminal domain of the repressor at fast timescales after complex ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635160 Mon, 09 Jan 2012 05:00:00 +0100 5635160 http://www.medworm.com/index.php?rid=5635159&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311009124%2Fabstract%3Frss%3Dyes Highlights: ► T82M mutation does not change contacts with UDPG and Tyr194 positioning. ► Autoglucosylation, DBM glucosylation and UDPG hydrolysis are abolished in T82M mutant. ► Glucose transfer activities are lost by Val but not by Ser substitution of Thr82.Abstract: The X-ray structure of rabbit glycogenin containing the T82M (T83M according to previous authors amino acid numbering ) mutation causing glycogenosis showed the loss of Thr82 hydrogen bond to Asp162, the residue involved in the activation step of the glucose transfer reaction mechanism. Autoglucosylation, maltoside transglucosylation and UDP-glucose hydrolyzing activities were abolished even though affinity and interactions with UDP-glucose and positioning of Tyr194 acceptor were conserved. Substitution of Thr82 for ser... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635159 Wed, 04 Jan 2012 05:00:00 +0100 5635159 http://www.medworm.com/index.php?rid=5635155&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008830%2Fabstract%3Frss%3Dyes Highlights: ► Lactoferrin (Lf) inhibits TNF-α-stimulated ICAM-1 expression in endothelial cells. ► Lf down-regulates TNF-α-stimulated ICAM-1 expression at the transcriptional level. ► Lf binds to the proximal NF-κB site in human ICAM-1 promoter in vitro and in vivo. ► Lf interferes with NF-κB for binding to the ICAM-1 promoter region.Abstract: Lactoferrin (Lf) is known to have anti-inflammatory activity, but the mechanisms of action by Lf remain to be elucidated. Here, we demonstrated that TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) was down-regulated by Lf in a DNA-binding dependent manner at transcriptional level in endothelial cells. Our results showed that Lf bound to a DNA region in the ICAM-1 promoter in vitro as well as in chromatin context. L... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635155 Tue, 03 Jan 2012 05:00:00 +0100 5635155 http://www.medworm.com/index.php?rid=5635151&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311009100%2Fabstract%3Frss%3Dyes Highlights: ► Oryza sativa GUN4, ChlI, ChlD, and ChlH reconstituted Mg-chelatase activity. ► Preactivation of ChlH with GUN4, protoporphyrin and Mg2+ gave maximum activity. ► Protoporphyrin omission during preactivation almost completely abolished activity. ► Protoporphyrin preincubation with OsChlH was most important for preactivation. ► GUN4’s C-terminal is essential for preactivation of ChlH but not porphyrin binding.Abstract: Oryza sativa GUN4 together with the magnesium chelatase subunits ChlI, ChlD, and ChlH have been heterologously expressed and purified to reconstitute magnesium chelatase activity in vitro. Maximum magnesium chelatase activity requires pre-activation of OsChlH with OsGUN4, Mg2+ and protoporphyrin-IX. OsGUN4 and OsChlH preincubated without protoporphyrin... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635151 Tue, 03 Jan 2012 05:00:00 +0100 5635151 http://www.medworm.com/index.php?rid=5635158&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311009112%2Fabstract%3Frss%3Dyes Highlights: ► SGLT are sodium-dependent sugar cotransporters. ► We cloned and functionally characterised a new family member SGLT5. ► We identified SGLT5 as a kidney specific mannose transporter.Abstract: Sodium glucose cotransporters (SGLT) actively catalyse carbohydrate transport across cellular membranes. Six of the 12 known SGLT family members have the capacity to bind and/or transport monosaccharides (SGLT-1 to 6); of these, all but SGLT-5 have been characterised. Here we demonstrate that human SGLT-5 is exclusively expressed in the kidney. Four splice variants were detected and the most abundant SGLT-5-mRNA was functionally characterised. SGLT-5 mediates sodium-dependent [14C]-α-methyl-d-glucose (AMG) transport that can be inhibited by mannose, fructose, glucose, and galactose... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635158 Mon, 02 Jan 2012 05:00:00 +0100 5635158 http://www.medworm.com/index.php?rid=5635152&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311009136%2Fabstract%3Frss%3Dyes Highlights: ► FLU is part of a protein complex bound to chloroplast membranes, primarily on the thylakoids. ► FLU co-migrates on BNGE with several enzymes of the chlorophyll biosynthesis pathway. ► FLU co-immunoprecipitates with CHL27, POR B, POR C and geranylgeranyl reductase. ► FLU co-immunoprecipitates with GluTR only in the dark.Abstract: Regulation of tetrapyrrole biosynthesis in higher plants has been attributed to negative feedback control. Two effectors of feedback inhibition have been identified, heme and the FLU protein. Inhibition by heme implicates the Fe-branch via regulation of the initial step of tetrapyrrole synthesis. In the present work a FLU-containing chloroplast membrane complex was identified, that besides FLU comprises the four enzymes catalyzing the final st... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635152 Mon, 02 Jan 2012 05:00:00 +0100 5635152 http://www.medworm.com/index.php?rid=5556643&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008969%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556643 Sun, 01 Jan 2012 22:28:12 +0100 5556643 http://www.medworm.com/index.php?rid=5635157&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311009094%2Fabstract%3Frss%3Dyes Highlights: ► Kinetic evaluation of chAPE1 metal ion specificity. ► Use of inhibitory and activating metal ion to probe for the catalytic mechanism. ► Two metal ion assisted catalysis describes best the mechanism of chAPE1. ► Crystal structures depict non-productive metal ion complexes with substrates and products.Abstract: The APE1, an important mammalian AP endonuclease, is an essential enzyme in the base excision DNA repair pathway (BER). The number of metal ions involved directly in the catalysis remains controversial. Here we describe the metal ion titration experiments that demonstrate the requirement for two metal ions for the endonuclease activity of the Chinese hamster APE1. The titration with the non-activating metal ion La3+ showed a biphasic behavior with activating and... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635157 Thu, 29 Dec 2011 05:00:00 +0100 5635157 http://www.medworm.com/index.php?rid=5635156&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100888X%2Fabstract%3Frss%3Dyes Highlights: ► Generation of non-oxidizable oleate-enriched cardiolipins via mitochondrial targeting. ► Desensitrization to apoptosis via suppression of cardiolipjn oxidation. ► Inhibition of acyl-CoA synthase reinstates polyunsaturation of cardiolipin. ► Inhibition of acyl-CoA synthase reinstates sensitivity to apoptosis.Abstract: Peroxidation of cardiolipin in mitochondria is essential for the execution of apoptosis. We suggested that integration of oleic acid into cardiolipin generates non-oxidizable cardiolipin species hence protects cells against apoptosis. We synthesized mitochondria-targeted triphenylphosphonium oleic acid ester. Using lipidomics analysis we found that pretreatment of mouse embryonic cells with triphenylphosphonium oleic acid ester resulted in decreased conte... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635156 Thu, 29 Dec 2011 05:00:00 +0100 5635156 http://www.medworm.com/index.php?rid=5635154&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008799%2Fabstract%3Frss%3Dyes Highlights: ► Splice blocking of sox31 elicits developmental arrest in zebrafish embryos. ► The Sb MO impairs the zygotic gene “up” and maternal mRNA “down” events during MBT. ► The Sb MO of sox31 induces an apoptotic response.Abstract: Here we report that splice blocking morpholinos (Sb MO) against zebrafish sox31 elicit developmental arrest, likely through creating a series of dominant negative splicing variants. Embryos injected with the Sb MO develop normally before the Mid-Blastula Transition (MBT); however, they do not initiate epiboly. Microarray analysis of mRNAs collected at the dome stage revealed that the Sb MO impairs activation of a large set of zygotic genes and reduces degradation of maternal mRNA during MBT. Furthermore, an apoptotic response occurs in Sb morp... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5635154 Thu, 29 Dec 2011 05:00:00 +0100 5635154 http://www.medworm.com/index.php?rid=5592665&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311009069%2Fabstract%3Frss%3Dyes Highlights: ► S100A8/A9 gene induction in keratinocytes by TLR3 ligand polyI:C. ► Confirmation in organotypic epithelial “raft” culture after herpes simplex virus infection. ► S100A8/A9 gene induction is not dependent on IL-10. ► Involvement of NF-κB, p38 MAPK, PI-3K and Jak-Stat signal transduction pathways in polyI:C-induced S100A8/A9 gene expression. ► S100A8/A9 gene induction is abrogated by treatment with either cycloheximide or bleomycin.Abstract: Viral double-stranded RNA (dsRNA) and its synthetic analog polyI:C are recognized via multiple pathways and induce the expression of genes related to inflammation. In the present study, we demonstrated the polyI:C-induced gene expression of the damage associated molecular pattern (DAMP) molecules S100A8 and S100A9, while othe... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592665 Thu, 29 Dec 2011 05:00:00 +0100 5592665 http://www.medworm.com/index.php?rid=5592662&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008878%2Fabstract%3Frss%3Dyes Highlights: ► We studied the role of 5-HT2B receptor (5-HT2BR) in cardiac hypertrophy in rats. ► Isoproterenol infusion for 28days was used to induce cardiac hypertrophy in rats. ► 5-HT2BR protein overexpression was seen in isoproterenol-induced cardiac hypertrophy. ► 5-HT2BR blockade ameliorated hypertrophy along with phosphorylation of Akt/GSK-3β/eNOS. ► GSK-3β inhibition further amplified the protective effect of 5-HT2BR blockade.Abstract: Herein, we studied the cross talk between 5-HT2B receptor blocker (SB-204741) and GSK-3β inhibitor (SB-216763) in isoproterenol-induced cardiac hypertrophy for 28days. SB-204741 treatment significantly ameliorated (P (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592662 Tue, 27 Dec 2011 05:00:00 +0100 5592662 http://www.medworm.com/index.php?rid=5592651&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008854%2Fabstract%3Frss%3Dyes In this study, the evolutionarily conserved intracellular adaptor protein, receptor of activated C kinase 1 (RACK1) was identified as a novel interaction partner of protein inhibitor of activated STAT 2 (PIAS2) using a yeast two-hybrid screening system. The direct interaction and co-localization of RACK1 with PIAS2 was confirmed by immunoprecipitation and immunofluorescence staining analysis, respectively. The 5th to 7th Trp-Asp 40 (5–7 WD40) repeats of RACK1 were identified as the minimal domain required for interaction with PIAS2 by deletion analysis. Furthermore, multiple PIAS2-domains, particularly the ‘PINIT’ and RLD domains, bind the RACK1 5–7 WD40 domain.Structured summary of protein interactions: PIAS2 physically interacts with RACK1 by two hybrid (View interaction)RACK1 an... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592651 Tue, 27 Dec 2011 05:00:00 +0100 5592651 http://www.medworm.com/index.php?rid=5592666&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008933%2Fabstract%3Frss%3Dyes The first sentence of Section 4.1, ‘The Vps4 complex‘ should read: From archeae to humans, Vps4 releases ESCRT-III subunits from membranes into the cytoplasm. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592666 Mon, 26 Dec 2011 05:00:00 +0100 5592666 http://www.medworm.com/index.php?rid=5592652&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008908%2Fabstract%3Frss%3Dyes Highlights: ► Hyperhomocysteinemia has been identified as an independent risk factor for the development of Alzheimer’s disease. ► Homocysteine can be converted to Hcy-thiolactone, which can alter protein structure by N-homocysteinylation. ► We examine changes in the structure and cytotoxicity of N-homocysteinylated amyloid beta peptide aggregation. ► The modification induces a change in structure and increases its tendency to form toxic aggregates.AbstractHyperhomocysteinemia has recently been identified as an important risk factor for Alzheimer’s disease (AD). One of the potential mechanisms underlying harmful effects of homocysteine (Hcy) is site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HCTL). The accumulation of amyloid β-peptide (Aβ)... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592652 Fri, 23 Dec 2011 05:00:00 +0100 5592652 http://www.medworm.com/index.php?rid=5592664&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100891X%2Fabstract%3Frss%3Dyes Highlights: ► Electron microscopic analyses prove the elimination of insulin receptors from caveolae in the state of insulin resistance. ► This was accompanied by a concomitant increase of ganglioside GM3 in adipocytes. ► Blocking of the GM3 increase restores the number of insulin receptors in caveolae.Abstract: Previously, we demonstrated that an inhibitor of ganglioside biosynthesis, d-PDMP, could restore impaired insulin signaling in tumor necrosis factor α (TNFα)-treated adipocytes by blocking the increase of GM3 ganglioside. Here, we analyzed the interaction between insulin receptor (IR) and GM3 in the plasma membranes using immunoelectron microscopy. In normal adipocytes, most GM3 molecules localized at planar and non-caveolar regions. Approximately 19% of IR molecules were d... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592664 Thu, 22 Dec 2011 05:00:00 +0100 5592664 http://www.medworm.com/index.php?rid=5592663&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008891%2Fabstract%3Frss%3Dyes Highlights: ► Amphiphilic peptides induce aggregation of a native-like protein. ► The peptide action resulted in morphologically distinct supramolecular structures. ► Amyloid-like assemblies were not detectable. ► The mechanism of peptide action is based on electrostatic and hydrophobic interactions.Abstract: A striking potential of the amphiphilic dipeptides, Arg-Phe or Asp-Phe, to induce aggregation of a model protein, alcohol dehydrogenase in its native-like state, has been demonstrated under physiologically relevant conditions, using dynamic light scattering, fluorescence spectroscopy, circular dichroism, transmission electron- and atomic force microscopy. The peptide action resulted in accumulation of a variety of morphologically distinct supramolecular structures profoundly d... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592663 Thu, 22 Dec 2011 05:00:00 +0100 5592663 http://www.medworm.com/index.php?rid=5592653&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008921%2Fabstract%3Frss%3Dyes Highlights: ► We identify homologies between the toxin domains of CDI systems and PF04740 proteins. ► Several PF04740 C-terminal domains have cytotoxic RNase activities. ► The activity of each PF04740 protein is specifically blocked by cognate antitoxin. ► We conclude that PF04740 proteins constitute a new toxin–antitoxin family.Abstract: The C-terminal regions (CT) of Pfam PF04740 proteins share significant sequence identity with the toxic CdiA-CT effector domains of contact-dependent growth inhibition (CDI) systems. In accord with this homology, we find that several PF04740 CT domains inhibit cell growth when expressed in Escherichia coli. This growth inhibition is specifically blocked by antitoxin proteins encoded downstream of each PF04740 gene. The YobL-CT, YxiD-CT and YqcG-... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592653 Thu, 22 Dec 2011 05:00:00 +0100 5592653 http://www.medworm.com/index.php?rid=5592661&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008842%2Fabstract%3Frss%3Dyes Highlights: ► ComX pheromone has prenylated tryptophan residue. ► Universality of this unique modification has not been elucidated. ► We established a cell-free system, whereby the tryptophan residue is geranylated. ► Using a cell-free system, we investigated enzymatic reaction conditions. ► This is the first report of in vitro geranylation on the tryptophan residue.Abstract: ComX pheromone is an isoprenoidal oligopeptide containing a modified tryptophan residue, which stimulates natural genetic competence in the gram-positive bacterium Bacillus. Since posttranslational prenylation on the tryptophan residue has not been reported except in ComX pheromone, the universality of this modification has not yet been elucidated. In this paper, we established a cell-free system, whereby th... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592661 Mon, 19 Dec 2011 05:00:00 +0100 5592661 http://www.medworm.com/index.php?rid=5592660&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008829%2Fabstract%3Frss%3Dyes Highlights: ► Use of 15N-labeling and mass spectrometry to determine half-life times of proteins. ► Half-life times of photosystem I and II proteins. ► Fast oligo/monomeric interchange in photosystems, or only one form exists in vivo. ► Small Cab-like proteins do not affect the half-life times of photosynthetic proteins.Abstract: The half-life times of photosystem I and II proteins were determined using 15N-labeling and mass spectrometry. The half-life times (30–75h for photosystem I components and (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592660 Mon, 19 Dec 2011 05:00:00 +0100 5592660 http://www.medworm.com/index.php?rid=5592658&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008805%2Fabstract%3Frss%3Dyes Highlights: ► The FMN-heme IET kinetics in full length and truncated oxygenase/FMN construct iNOS proteins were determined at 283–304K. ► This is the first study of temperature dependence of the NOS IET kinetics. ► Eyring equation was used to analyze the temperature dependence data. ► The magnitude of activation entropy for the IET in the oxygenase/FMN construct is only one-fifth of that for the holoenzyme. ► The results indicate that the FMN domain in the holoenzyme needs to sample more conformations before the IET takes place.Abstract: The FMN-heme interdomain (intraprotein) electron transfer (IET) kinetics in full length and oxygenase/FMN (oxyFMN) construct of human iNOS were determined by laser flash photolysis over the temperature range from 283 to 304K. An appreciable inc... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592658 Mon, 19 Dec 2011 05:00:00 +0100 5592658 http://www.medworm.com/index.php?rid=5592650&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100874X%2Fabstract%3Frss%3Dyes Highlights: ► Human Bax physically interacts with mammalian and yeast Tom22. ► A peptide corresponding to the receptor domain of Tom22 stimulates Bax translocation. ► This peptide favors an inactive conformation of Bax. ► This peptide favors a dimeric form of Bax at the expense of the oligomeric form.Abstract: The role of the mitochondrial protein receptor Tom22p in the interaction of pro-apoptotic protein Bax with yeast mitochondria was investigated. Co-immunoprecipitation assays showed that human Bax interacted with different TOM subunits, including Tom22p. Expression of the cytosolic receptor domain of human Tom22 increased Bax mitochondrial localization, but decreased the proportion of active Bax. BN–PAGE showed that the cytosolic domain of Tom22 interfered with the oligomeri... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592650 Mon, 19 Dec 2011 05:00:00 +0100 5592650 http://www.medworm.com/index.php?rid=5592659&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008817%2Fabstract%3Frss%3Dyes Abstract: We previously demonstrated that 14-3-3σ was downregulated in 5-fluorouracil (5-Fu)-resistant MCF-7 breast cancer cells (MCF-7/5-Fu). Here, we found that stably enhanced 14-3-3σ expression strengthened the effects of 5-Fu, Mitoxantrone and cDDP. 14-3-3σ stabilised the p53 protein and bound Akt to inhibit its activity and its downstream targets: survivin, Bcl-2 and NF-κB-p50. In addition, decreased p53 expression, but not promoter hypermethylation, was responsible for the downregulation of 14-3-3σ in MCF-7/5-Fu cells. Meanwhile, initial treatments with high concentrations of 5-Fu clearly induced 14-3-3σ and p53 expression in a time-dependent manner. 14-3-3σ-mediated molecular events that synergise with p53 may play important roles in the chemotherapy of breast cancer. (Sourc... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592659 Fri, 16 Dec 2011 05:00:00 +0100 5592659 http://www.medworm.com/index.php?rid=5592657&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008787%2Fabstract%3Frss%3Dyes Highlights: ► Solvent-exposed tyrosines 46 and 48 of cytochrome c are nitrated in vitro. ► Nitration of cytochrome c does not affect the reaction with cytochrome c oxidase. ► Nitration of cytochrome c impairs its ability to activate caspase-9.Abstract: Under nitroxidative stress, a minor fraction of cytochrome c can be modified by tyrosine nitration. Here we analyze the specific effect of nitration of tyrosines 46 and 48 on the dual role of cytochrome c in cell survival and cell death. Our findings reveal that nitration of these two solvent-exposed residues has a negligible effect on the rate of electron transfer from cytochrome c to cytochrome c oxidase, but impairs the ability of the heme protein to activate caspase-9 by assembling a non-functional apoptosome. It seems that cytochr... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592657 Fri, 16 Dec 2011 05:00:00 +0100 5592657 http://www.medworm.com/index.php?rid=5592656&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008775%2Fabstract%3Frss%3Dyes Highlights: ► Capacitation and cyclic nucleotides increase the macroscopic current in mouse sperm. ► There are subpopulations of sperm depending on their response to cyclic nucleotides. ► CNG channels are physiologically active in the mature mouse sperm. ► Sperm CNG channels have different sensitivity between cGMP and cAMP. ► CNG channels participate in sperm capacitation providing an entry pathway for Ca2+.Abstract: During capacitation of mammalian sperm intracellular [Ca2+] and cyclic nucleotides increase, suggesting that CNG channels play a role in the physiology of sperm. Here we study the effect of capacitation, 8Br-cAMP (8-bromoadenosine 3′,5′-cyclic monophosphate) and 8Br-cGMP (8-bromoguanosine 3′,5′-cyclic monophosphate) on the macroscopic ionic currents of mouse ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592656 Fri, 16 Dec 2011 05:00:00 +0100 5592656 http://www.medworm.com/index.php?rid=5556662&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008763%2Fabstract%3Frss%3Dyes Highlights: ► HPV E7 viral oncoprotein ablates L1MdA5 reactivation following genotoxic stress. ► HPV E7 disrupts retinoblastoma-mediated L1MdA5 promoter transactivation. ► The basal and carcinogen-induced activities of L1MdA5 promoter are independent of Rb repressor function. ► HPV E7 disrupts assembly of protein complexes regulating L1MdA5.Abstract: Murine L1Md-A5 retrotransposon is a redox-inducible element regulated by Nrf-2/JunD and E2F/Rb-binding sites within its promoter (5′-UTR). Because the human papillomavirus (HPV) oncoprotein E7 interacts with retinoblastoma (pRb) and members of the AP1 family, studies were conducted to examine functional interactions between HPV E7, pRb, and histone deacetylase 2 (HDAC2) in the regulation of L1Md-A5. Using a transient heterologous tra... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556662 Mon, 12 Dec 2011 05:00:00 +0100 5556662 http://www.medworm.com/index.php?rid=5556661&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008751%2Fabstract%3Frss%3Dyes Highlights: ► We solve by mass spectrometry the structure of two pyoverdine siderophore precursors. ► A PvdQ mutant produces these precursors. ► They both have a higher molecular mass as the pyoverdine. ► We show that both compounds contain an unformed chromophore and a myristic or a myristoleic acid chain.Abstract: Pyoverdine I (PVDI) is the major siderophore produced by Pseudomonas aeruginosa to import iron. Biosynthesis of this chelator involves non-ribosomal peptide synthetases and other enzymes. PvdQ is a periplasmic enzyme from the NTN hydrolase family and is involved in the final steps of PVDI biosynthesis. A pvdQ mutant produces two non-fluorescent PVDI precursors with a higher molecular mass than PVDI. In the present study, we describe the use of mass spectrometry to deter... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556661 Mon, 12 Dec 2011 05:00:00 +0100 5556661 http://www.medworm.com/index.php?rid=5592649&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008738%2Fabstract%3Frss%3Dyes In this study, we discover and report the enzymatic target of BoNT/F5. ► Using mass spectrometry, we determine that BoNT/F5 cleaves synaptobrevin-2. ► BoNT/F5 cleaves synaptobrevin-2 between 91L and 92E. ► Synaptobrevin-2 cleavage between 91L and 92E is a novel site for any BoNT cleavage.Abstract: Botulinum neurotoxins (BoNTs) cause botulism by cleaving proteins necessary for nerve transmission. There are seven serotypes of BoNT, A–G, characterized by their response to antisera. Many serotypes are further distinguished into differing subtypes based on amino acid sequence, some of which result in functional differences. Our laboratory previously reported that all tested subtypes within each serotype have the same site of enzymatic activity. Recently, three new subtypes of BoNT/F; /F... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592649 Fri, 09 Dec 2011 05:00:00 +0100 5592649 http://www.medworm.com/index.php?rid=5556654&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008623%2Fabstract%3Frss%3Dyes Highlights: ► Mutational and functional studies identified 11 residues critical for SepCysS activity. ► All three active site cysteines of SepCysS are essential for tRNA-dependent Cys formation. ► The phosphate group of Sep is recognized by Arg79, His103 and Tyr104.Abstract: In methanogenic archaea, Sep-tRNA:Cys-tRNA synthase (SepCysS) converts Sep-tRNACys to Cys-tRNACys. The mechanism of tRNA-dependent cysteine formation remains unclear due to the lack of functional studies. In this work, we mutated 19 conserved residues in Methanocaldococcus jannaschii SepCysS, and employed an in vivo system to determine the activity of the resulting variants. Our results show that three active-site cysteines (Cys39, Cys42 and Cys247) are essential for SepCysS activity. In addition, combined with s... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556654 Fri, 09 Dec 2011 05:00:00 +0100 5556654 http://www.medworm.com/index.php?rid=5556653&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008611%2Fabstract%3Frss%3Dyes Highlights: ► Sulindac and its two metabolites equally inhibit aldose reductase in vitro. ► Crystal structures of sulindacs and tolmetin in complex with aldose reductase. ► Sulindac and its two metabolites have the same binding modes with aldose reductase. ► π–π Stacking favored by sulindac and Phe122 is pivotal to its high inhibition.Abstract: Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear beneficial clinical effects on Type 2 diabetes. However, the molecular basis for these properties is unclear. Here, we report that SLD and its pharmacologically active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un-competitive inhibitors of AR in vit... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556653 Fri, 09 Dec 2011 05:00:00 +0100 5556653 http://www.medworm.com/index.php?rid=5556650&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008581%2Fabstract%3Frss%3Dyes Highlights: ► A novel selection marker system based on the metabolism of d-lactate was developed. ► At high d-lactate concentrations wild-type development is arrested after germination. ► Plants overexpressing d-lactate dehydrogenase detoxify d-lactate and survive. ► d-LDH was established as marker in Arabidopsis thaliana allowing selection after germination. ► Selection on d-lactate adds a marker system as a good alternative to traditional ones.Abstract: d-Lactate negatively affects Arabidopsis thaliana seedling development in a concentration-dependent manner. At media d-lactate concentrations greater than 5–10mM the development of wild-type plants is arrested shortly after germination whereas plants overexpressing the endogenous d-lactate dehydrogenase (d-LDH) detoxify d-lact... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556650 Fri, 09 Dec 2011 05:00:00 +0100 5556650 http://www.medworm.com/index.php?rid=5592655&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008726%2Fabstract%3Frss%3Dyes Highlights: ► Sensitivity of yeast frataxin-deficient cells to hydrogen peroxide is partially mediated by metacaspase. ► In the absence of metacaspase, frataxin-deficient cells recover antioxidant capacity and heme biosynthesis. ► Metacaspase is implicated in mitochondrial energy metabolism and intracellular redox control.Abstract: Friedreich ataxia is the most common recessive neurodegenerative disease and is caused by reduced expression of mitochondrial frataxin. Frataxin depletion causes impairment in iron–sulfur cluster and heme biosynthesis, disruption of iron homeostasis and hypersensitivity to oxidants. Currently no pharmacological treatment blocks disease progression, although antioxidant therapies proved to benefit patients. We show that sensitivity of yeast frataxin-defic... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592655 Wed, 07 Dec 2011 05:00:00 +0100 5592655 http://www.medworm.com/index.php?rid=5592654&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008702%2Fabstract%3Frss%3Dyes Highlights: ► Low-dose ethanol rapidly upregulates ALDH2 activity to maintain the balance of the redox status. ► ALDH2 mediates ethanol-induced eNOS activation by preventing ROS accumulation. ► Ethanol-induced ALDH2 activation is dependent on acetylation by SIRT3 inactivation. ► Ethanol-induced SIRT3 inactivation is due to a reduced NAD+/NADH ratio in mitochondria.Abstract: Moderate alcohol consumption has beneficial effects on endothelial nitric-oxide synthase (eNOS) activation, which can engender an array of anti-atherogenic actions. Here we show that in human aortic endothelial cells (HAECs), rapid activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) mediates ethanol-induced eNOS activation by preventing reactive oxygen species (ROS) accumulation. Furthermore, activation... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5592654 Wed, 07 Dec 2011 05:00:00 +0100 5592654 http://www.medworm.com/index.php?rid=5556664&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008696%2Fabstract%3Frss%3Dyes Two tables () are missing in the original text. Part 3.2: (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556664 Wed, 07 Dec 2011 05:00:00 +0100 5556664 http://www.medworm.com/index.php?rid=5556646&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008714%2Fabstract%3Frss%3Dyes Highlights: ► Inhibition of GSK3 results in translocation of FBPase to mitochondria. ► FBPase reduces Ca2+-induced mitochondrial swelling. ► FBPase influences mitochondrial ATP synthesis.Abstract: A growing body of research suggests that fructose 1,6-bisphosphatase (FBPase) might be involved in regulation of cell mortality/survival. However, the precise role of FBPase in the process remains unknown. Here, we show for the first time that in HL-1 cardiomyocytes, inhibition of glycogen synthase kinase-3 results in translocation of FBPase to mitochondria. In vitro experiments demonstrate that FBPase reduces the rate of calcium-induced mitochondrial swelling, affects ATP synthesis and interacts with mitochondrial proteins involved in regulation of volume and energy homeostasis. We suggest... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556646 Wed, 07 Dec 2011 05:00:00 +0100 5556646 http://www.medworm.com/index.php?rid=5556660&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008684%2Fabstract%3Frss%3Dyes Abstract: Latrunculin depolymerizes and jasplakinolide polymerizes β-cell actin microfilaments. Both increase insulin secretion when Ca2+ enters β-cells during depolarization by glucose, sulfonylureas or potassium. Mouse islets were held hyperpolarized with diazoxide, and stimulated with acetylcholine to test the role of microfilaments in insulin secretion triggered by intracellular Ca2+ mobilization and store-operated Ca2+ entry (SOCE).Jasplakinolide slightly attenuated Ca2+ mobilization and did not affect SOCE, but consistently inhibited the attending insulin secretion. Latrunculin did not affect Ca2+ changes induced by acetylcholine, but consistently increased insulin secretion, its effect being larger in response to Ca2+ entry than to Ca2+ mobilization. Microfilaments have thus a dis... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556660 Mon, 05 Dec 2011 05:00:00 +0100 5556660 http://www.medworm.com/index.php?rid=5556659&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008672%2Fabstract%3Frss%3Dyes Highlights: ► We prepared transplastomic tobacco expressing the nuclear Whirly1 gene in plastids. ► Tagged Whirly1 produced by plastids translocates into the nucleus. ► In the nucleus tagged Whirly1 induces expression of pathogen response genes.Abstract: Whirly1 was shown to be dually located in chloroplasts and nucleus of the same cell. To investigate whether the protein translocates from chloroplasts to the nucleus, we inserted a construct encoding an HA-tagged Whirly1 into the plastid genome of tobacco. Although the tagged protein was synthesized in plastids, it was detected in nuclei. Dual location of the protein was confirmed by immunocytological analyses. These results indicate that the plastidial Whirly1 is translocated from the plastid to the nucleus where it affects expressi... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556659 Mon, 05 Dec 2011 05:00:00 +0100 5556659 http://www.medworm.com/index.php?rid=5556658&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008660%2Fabstract%3Frss%3Dyes Abstract: Site-specific protein cleavage is a ubiquitous process in cellular protein metabolism, yet molecular tools to provide control of protein cleavage inside living cells remain scarce. Here, we show that the C-terminal intein fragment of the non-canonical Ssp (Synechocystis sp. PCC6803) DnaB S1 split-intein can be used as a site-specific protease for in vivo protein cleavage both in bacterial and eukaryotic cells. Mutagenesis data indicate a broad tolerance of the intein-derived protease (IP) toward the amino acid upstream of the cleavage site. Furthermore, deletion studies reveal that the recognition sequence for the IP can be as short as ten amino acids. The structural features underlying the cleavage reaction preclude unintended proteolysis of endogenous proteins, thus ensuring th... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556658 Mon, 05 Dec 2011 05:00:00 +0100 5556658 http://www.medworm.com/index.php?rid=5464916&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008477%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464916 Fri, 02 Dec 2011 07:36:11 +0100 5464916 http://www.medworm.com/index.php?rid=5556657&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008659%2Fabstract%3Frss%3Dyes Highlights: ► We study the conformational changes induced by partial ligation of hemoglobin. ► Sulfhydryl reactions of β93Cys in metal hybrid hemoglobins are measured. ► All diliganded species show similar or higher reactivity than the final state. ► Both asymmetrical diliganded tetramers exhibit a slight symmetry distortion.Abstract: To investigate the conformational changes in human tetrameric (αβ)2 hemoglobin upon binding of the first two ligands, we have measured the kinetics of reactions between 4,4′-dithiodipyridine and β93Cys sulfhydryl groups of four diliganded hemoglobins by using CO-bound Fe(II)–Ni(II) hybrids with and without β-β cross-linking. The data show that all the diliganded intermediates have high sulfhydryl reactivities, which are greater than or equal... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556657 Fri, 02 Dec 2011 05:00:00 +0100 5556657 http://www.medworm.com/index.php?rid=5556656&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008647%2Fabstract%3Frss%3Dyes Highlights: ► CI analysis allows comparison among proteins of different sizes. ► CI is computed for NC, PMG and MG intrinsically disordered proteins. ► Sequence length unspecifically modulates compaction within each group. ► Cooperative character of the weak interactions leading to chain collapse.Abstract: This work investigates the effect of chain length on the degree of compaction of intrinsically disordered proteins (IDPs). The three main IDP types, native coil (NC), pre-molten globule (PMG) and molten globule (MG), are compared by means of a compaction index (CI) normalized for chain length. The results point out a strong variability of compactness as a function of chain length within each group, with larger proteins populating more compact states. While qualitative sequence fe... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556656 Tue, 29 Nov 2011 05:00:00 +0100 5556656 http://www.medworm.com/index.php?rid=5556655&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008635%2Fabstract%3Frss%3Dyes Highlights: ► We tested the impact of a protein chaperone on mRNA association with mitochondria. ► We found that altered activity of Ssa1 affected mRNA localization. ► Genome-wide analysis revealed that many affected mRNAs encode hydrophobic proteins. ► The mitochondrial receptor Tom70 is important for Ssa1 function. ► We propose that Ssa1 mediates mRNA transport while the mRNA is translated.Abstract: Many nuclear-transcribed mRNAs encoding mitochondrial proteins are localized near the mitochondrial outer membrane. A yet unresolved question is whether protein synthesis is important for transport of these mRNAs to their destination. Herein we present a connection between mRNA localization in yeast and the protein chaperone Ssa1. Ssa1 depletion lowered mRNA association with mitocho... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556655 Tue, 29 Nov 2011 05:00:00 +0100 5556655 http://www.medworm.com/index.php?rid=5556652&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100860X%2Fabstract%3Frss%3Dyes Highlights: ► Detection of tau in the extracellular environment. ► Secretion of excess of tau protein as a mechanism to avoid toxicity. ► Tau is released in association with microvesicles.Abstract: Increasing amounts of tau protein were expressed in non-neuronal cells. When intracellular amounts reached a threshold level, tau protein was released to the extracellular culture medium in association with membrane vesicles. Hence, we propose that tau might be secreted through membrane vesicles as a cellular mechanism to eliminate the excess of tau protein, thereby avoiding its toxicity. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556652 Tue, 29 Nov 2011 05:00:00 +0100 5556652 http://www.medworm.com/index.php?rid=5556651&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008593%2Fabstract%3Frss%3Dyes Highlights: ► Overexpression of TTP inhibits IL-17 production in human T cells. ► TTP binds to the ARE within the IL-17 3′UTR. ► TTP enhances the decay of IL-17 mRNA. ► TTP can be a novel target to control IL-17 production.Abstract: An excess of interleukin 17 (IL-17) may contribute to chronic inflammatory disorders, but mechanisms that regulate IL-17 in immune cells are unclear. Here we report that tristetraprolin (TTP) inhibits IL-17 production in human T cell lines. Overexpression of TTP decreased the expression of IL-17. Conversely, TTP inhibition by siRNA increased IL-17 production. IL-17 mRNA contains eight AREs within its 3′UTR. TTP bound directly to the IL-17 mRNA 3′UTR at a location between the fourth and seventh AREs and enhanced decay of IL-17 transcripts. These re... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556651 Tue, 29 Nov 2011 05:00:00 +0100 5556651 http://www.medworm.com/index.php?rid=5556649&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100843X%2Fabstract%3Frss%3Dyes Highlights: ► Iron regulatory proteins (IRPs) act by binding iron responsive elements (IREs). ► We show that the IRP1 binds the TfR B and Ftn H IREs with the same affinity. ► We solved the structure of the IRP1 in complex with the TfR 1 B IRE. ► The TfR B and Ftn H IREs bind IRP1 with different stem-loop conformations. ► Thus binding of different IREs depends on protein and RNA conformational plasticity.Abstract: Iron responsive elements (IREs) are short stem-loop structures found in several mRNAs encoding proteins involved in cellular iron metabolism. Iron regulatory proteins (IRPs) control iron homeostasis through differential binding to the IREs, accommodating any sequence or structural variations that the IREs may present. Here we report the structure of IRP1 in complex with ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556649 Thu, 24 Nov 2011 05:00:00 +0100 5556649 http://www.medworm.com/index.php?rid=5556648&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008428%2Fabstract%3Frss%3Dyes In this study we report the effects of KATP inhibitors on gap junction activity. ► Gap junction communication has been linked to the activity of KATP channels. ► KATP inhibitors with SUR2 specificity increase gap junction communication. ► We demonstrate these effects are independent of SUR2 expression.Abstract: Gap junctional intercellular communication (GJIC) regulates cellular homeostasis by propagating signaling molecules, exchanging cellular metabolites, and coupling electrical signals. In cancer, cells exhibit altered rates of GJIC which may play a role in neoplastic progression. KATP channels help maintain membrane polarity and linkages between KATP channel activity and rates of GJIC have been established. The mechanistic relationship has not been fully elucidated. We report th... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556648 Thu, 24 Nov 2011 05:00:00 +0100 5556648 http://www.medworm.com/index.php?rid=5556645&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008441%2Fabstract%3Frss%3Dyes Highlights: ► We used BiFC assays to study the interaction between huntingtin and α-synuclein. ► Huntingtin and α-synuclein interact, heterodimerize and co-aggregate. ► Huntingtin modifies α-synuclein intracellular distribution. ► Huntingtin and α-synuclein modify each other’s pattern of aggregation. ► Protein co-aggregation is relevant in many neurodegenerative disorders.Abstract: Several neurodegenerative disorders are characterized by the accumulation of proteinaceous inclusions in the central nervous system. These inclusions are frequently composed of a mixture of aggregation-prone proteins. Here, we used a bimolecular fluorescence complementation assay to study the initial steps of the co-aggregation of huntingtin (Htt) and α-synuclein (α-syn), two aggregation-prone ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556645 Thu, 24 Nov 2011 05:00:00 +0100 5556645 http://www.medworm.com/index.php?rid=5437073&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008131%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5437073 Wed, 23 Nov 2011 06:44:54 +0100 5437073 http://www.medworm.com/index.php?rid=5464926&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008404%2Fabstract%3Frss%3Dyes Highlights: ► SET is not only resistant to α1-antitrypsin, but also inactivates α1-antitrypsin. ► SET hydrolyzes the Met–Ser bond in the reaction center loop of α1-antitrypsin. ► α1-Antitrypsin is entirely the substrate for SET.Abstract: Streptomyces erythraeus trypsin (SET) is a serine protease that is secreted extracellularly by S. erythraeus. We investigated the inhibitory effect of α1-antitrypsin on the catalytic activity of SET. Intriguingly, we found that SET is not inhibited by α1-antitrypsin. Our investigations into the molecular mechanism underlying this observation revealed that SET hydrolyzes the Met–Ser bond in the reaction center loop of α1-antitrypsin. However, SET somehow avoids entrapment by α1-antitrypsin. We also confirmed that α1-antitrypsin loses its ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464926 Tue, 22 Nov 2011 05:00:00 +0100 5464926 http://www.medworm.com/index.php?rid=5556644&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008234%2Fabstract%3Frss%3Dyes Highlights: ► mFadA forms uniformly long and thin filaments with no binding activity. ► FadAc forms heterogeneous structures, due to the presence of pre-FadA. ► Heterogeneity of the FadA structure correlates with function. ► Shorter filaments may be the active form of FadA. ► First demonstration that signal peptide involved in adhesin assembly.Abstract: FadA, a novel adhesin of periodontal pathogen Fusobacterium nucleatum is composed of two forms, pre-FadA and mature FadA (mFadA), constituting the functional FadA complex (FadAc). By electron microscopy, we observed that mFadA formed uniformly long and thin filaments, while FadAc formed heterogeneous filaments of varying lengths and widths, as well as “knots”. Mutants in signal peptide or in the non-alpha-helical loop retainin... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556644 Mon, 21 Nov 2011 05:00:00 +0100 5556644 http://www.medworm.com/index.php?rid=5464946&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008416%2Fabstract%3Frss%3Dyes Highlights: ► Several different acyl chains can occupy the sn-1 position of good DAG substrates. ► 18:2 and 20:4 are only chains possible at sn-2 of good DAG substrates. ► The best substrate is the PI-cycle intermediate 18:0/20:4-DAG. ► 20:4/20:4-DAG surprisingly has equivalent activity to 18:0/20:4-DAG.Abstract: We show that diacylglycerol kinase-ε (DGKε) has less preference for the acyl chain at the sn-1 position of diacylglycerol (DAG) than the one at the sn-2 position. Although DGKε discriminates between 1-stearoyl-2-arachidonoyl-DAG and 1-palmitoyl-2-arachidonoyl-DAG, it has similar substrate preference for 1-stearoyl-2-arachidonoyl-DAG and 1,2-diarachidonoyl-DAG. We suggest that in addition to binding to the enzyme, the acyl chain at the sn-1 position may contribute to the... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464946 Mon, 21 Nov 2011 05:00:00 +0100 5464946 http://www.medworm.com/index.php?rid=5464944&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008374%2Fabstract%3Frss%3Dyes In conclusion, these data suggest that UCP3 may have a role in the protection of mitochondria against lipid-induced mitochondrial dysfunction, but only after long-term exposure to high-fat. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464944 Mon, 21 Nov 2011 05:00:00 +0100 5464944 http://www.medworm.com/index.php?rid=5464927&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008362%2Fabstract%3Frss%3Dyes Highlights: ► Protein kinase D (PKD) regulates the cardiac L-type voltage-gated calcium channel. ► We mutate the putative targets (S1884, S1930) of PKD on human cardiac L-type channel. ► We measure expression, phosphorylation and activity of L-type channel WT and mutants. ► S1884 is the functional targets of PKD on the human cardiac L-type channel.Abstract: Protein kinase D (PKD) regulates the activity of the L-type calcium channel in rat ventricular cardiomyocytes. However, the functional target residues of PKD on the L-type calcium channel remain to be identified. Our aim was to identify the functional phosphorylation sites of PKD on the human L-type calcium channel. The pore subunit of the human CaV1.2 (hCaV1.2) was stably expressed in HEK293 cells. Both the expression of a domi... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464927 Thu, 17 Nov 2011 05:00:00 +0100 5464927 http://www.medworm.com/index.php?rid=5464945&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008398%2Fabstract%3Frss%3Dyes Highlights: ► We investigated the link between osteogenic differentiation and cell migration. ► The motility of progenitor cells dramatically changed during differentiation. ► A mesenchymal mode of cell migration was promoted by inhibition of ROCK signaling. ► Upregulated migration of progenitor cells increased ectopic bone formation in vivo. ► Our findings may lead to a new therapeutic strategy for bone formation.Abstract: We showed that the migration, morphology and adhesiveness of undifferentiated mesenchymal cells dramatically changed during osteogenic differentiation. The migration of these cells was transiently upregulated early in osteogenic differentiation. At a later stage, migration was decreased but adhesiveness was increased. Furthermore, Cdc42 and Rac1 Rho-family sma... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464945 Wed, 16 Nov 2011 05:00:00 +0100 5464945 http://www.medworm.com/index.php?rid=5464925&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008386%2Fabstract%3Frss%3Dyes Highlights: ► S. cerevisiae telomerase (Est2) and Rvb1 and Rvb2 physically associate. ► Rvb2 was present in telomeric chromatin following immunoprecipitation under cross link conditions. ► Rvb2 still associated with Est2 in cells in which telomerase/Est2 could not be recruited at telomeric ends. ► rvb2 mutant alleles conferring slight, but stable, telomere shortening could be isolated.Abstract: Telomerase is a reverse transcriptase that maintains linear telomeres at a constant length. Here, we report that in the budding yeast Saccharomyces cerevisiae, Rvb2, a highly conserved member of the AAA+ family of ATPases, physically associates with telomerase/Est2 in vivo, both expressed from their endogenous promoter. Importantly, in genetic settings leading to a failure to recruit telomer... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464925 Wed, 16 Nov 2011 05:00:00 +0100 5464925 http://www.medworm.com/index.php?rid=5556663&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008350%2Fabstract%3Frss%3Dyes The correct name of the first author of reference 21 is Bunaciu, R.P. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5556663 Tue, 15 Nov 2011 05:00:00 +0100 5556663 http://www.medworm.com/index.php?rid=5464948&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008349%2Fabstract%3Frss%3Dyes In the body of the text, the lane descriptions for Fig. 2 are incorrect. More specifically, lanes 1, 2, 3, 4, 5 and 6 referred to in the text actually correspond to lanes 2, 3, 4, 5, 6 and 7 in the figure itself. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464948 Tue, 15 Nov 2011 05:00:00 +0100 5464948 http://www.medworm.com/index.php?rid=5464935&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007952%2Fabstract%3Frss%3Dyes In this study, we have performed a systematic nuclear magnetic resonance (NMR) investigation to study the sequence context effect on the pairing modes of T·T mismatches. Our results reveal for the first time that preferential pairing mode does exist in T·T mismatches with specific type of flanking base pairs. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464935 Tue, 15 Nov 2011 05:00:00 +0100 5464935 http://www.medworm.com/index.php?rid=5464943&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008337%2Fabstract%3Frss%3Dyes Highlights: ► HIV-1 Rev protein activates HCV gene expression. ► HIV-1 Rev directly interacts with the 5′-untranslated region (5′-UTR) of HCV RNA. ► Rev protein specifically binds to the internal loop (IIIb) of HCV 5′-UTR. ► Rev stimulates translation under the control of HCV 5′-UTR. ► HIV-1 Rev directly binds to HCV 5′-UTR to activate HCV gene expression.Abstract: Coinfection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) accelerates hepatitis C disease progression; however, the mechanism underlying this effect is unknown. Here, we investigated the role of HIV-1 in HCV gene expression and the mechanism involved in this regulation. We discovered that HIV-1 Rev protein activates HCV gene expression. We further revealed that Rev binds to the inter... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464943 Mon, 14 Nov 2011 05:00:00 +0100 5464943 http://www.medworm.com/index.php?rid=5464942&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008325%2Fabstract%3Frss%3Dyes Highlights: ► The chromophore in the long-lived intermediate of ChR2-C128T is a free retinal. ► It differs from the reduced-retro form of bacteriorhodopsin despite similar UV spectra. ► The photocycle of ChR2-C128T involves a transient cleavage of the retinal–protein linkage.Abstract: The photocycle of the light-activated channel, channelrhodopsin-2 C128T, has been studied by resonance Raman (RR) spectroscopy focussing on the intermediates P380 and P353 that constitute a side pathway in the recovery of the parent state. The P353 species displays a UV–vis absorption spectrum with a fine-structure reminiscent of the reduced-retro form of bacteriorhodopsin, whereas the respective RR spectra differ substantially. Instead, the RR spectra of the P380/P353 intermediate couple are closel... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464942 Mon, 14 Nov 2011 05:00:00 +0100 5464942 http://www.medworm.com/index.php?rid=5464941&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008313%2Fabstract%3Frss%3Dyes Highlights: ► We cut actin stress fibers located over the nucleus using laser nanoscissors. ► We investigated the dynamic behavior of stress fibers, nucleus, and intranuclear DNA. ► The nucleus moved after stress fiber dissection and showed marked local deformation. ► The distribution of intranuclear DNA near the dissected stress fibers changed. ► Stress fibers stabilize the position of DNA through connection with the nucleus.Abstract: Actin stress fibers (SFs) running across the top surface of the nucleus in vascular smooth muscle cells were dissected using laser nano-dissection technique to release its pretension, and the dynamic behavior of SFs, nucleus, and intranuclear DNA were investigated. SFs shortened across the top surface of the nuclei after their dissection. The nucle... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464941 Mon, 14 Nov 2011 05:00:00 +0100 5464941 http://www.medworm.com/index.php?rid=5464940&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008301%2Fabstract%3Frss%3Dyes This study biochemically confirmed vitamin E biosynthesis in the malaria parasite, which can be inhibited by usnic acid. Furthermore, we found evidence pointing to a role of this vitamin in infected erythrocytes. These findings not only contribute to current understanding of P. falciparum biology but also reveal a pathway that could serve as a chemotherapeutic target. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464940 Mon, 14 Nov 2011 05:00:00 +0100 5464940 http://www.medworm.com/index.php?rid=5396438&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008003%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396438 Fri, 11 Nov 2011 07:28:23 +0100 5396438 http://www.medworm.com/index.php?rid=5464939&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008295%2Fabstract%3Frss%3Dyes Highlights: ► A2AR, P2Y1R and P2Y12R are predominantly expressed on human platelets. ► Hetero-oligomerization between these three receptors has been shown to occur. ► Ca2+ signaling of P2Y1R agonist was inhibited by the A2AR and the P2Y12R antagonists. ► It was confirmed that this inhibition was mediated through these receptors.Abstract: A2A adenosine receptor (A2AR), P2Y1 receptor (P2Y1R) and P2Y12 receptor (P2Y12R) are predominantly expressed on human platelets. The individual role of each of these receptors in platelet aggregation has been actively reported. Previously, hetero-oligomerization between these three receptors has been shown to occur. Here, we show that Ca2+ signaling evoked by the P2Y1R agonist, 2-methylthioladenosine 5’ diphosphate (2MeSADP) was significantly inh... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464939 Fri, 11 Nov 2011 05:00:00 +0100 5464939 http://www.medworm.com/index.php?rid=5464938&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100826X%2Fabstract%3Frss%3Dyes Highlights: ► Intrinsic fluorescence of DNA increases upon G-quadruplex formation. ► Folding/unfolding of a G-quadruplex can be monitored by its intrinsic fluorescence. ► Fluorescence spectroscopy gives information on G-quadruplex structure and stability.Abstract: We characterized and compared the fluorescence properties of various well-defined G-quadruplex structures. The increase of intrinsic fluorescence of G-rich DNA sequences when they form G-quadruplexes can be used to monitor the folding and unfolding of G-quadruplexes as a function of cations and temperature. The temperature-dependent fluorescence spectra of different G-quadruplexes also exhibit characteristic patterns. Thus, the stability and possibly also the structure of G-quadruplexes can be characterized and distinguishe... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464938 Fri, 11 Nov 2011 05:00:00 +0100 5464938 http://www.medworm.com/index.php?rid=5464937&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008258%2Fabstract%3Frss%3Dyes Highlights: ► Hepatitis B virus replicates via reverse transcription. ► HBV polymerase contains the terminal protein domain at its N-terminus. ► The hydrophobic residues (Y, W, and I) of the terminal protein domain were analyzed. ► The data showed that the W74 and Y147 are important for viral DNA synthesis. ► The data showed that Y173 is important for RNA encapsidation.Abstract: Hepatitis B virus (HBV) replicates its DNA genome via reverse transcription. Precise roles of the terminal protein domain of HBV polymerase remain unknown. To gain insight, we created alanine substitution mutations at hydrophobic residues (i.e., tyrosine, tryptophan, and isoleucine), and then examined the extent by which these mutants carry out viral genome replication. Evidence indicated that three hydro... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464937 Fri, 11 Nov 2011 05:00:00 +0100 5464937 http://www.medworm.com/index.php?rid=5464936&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008246%2Fabstract%3Frss%3Dyes In this study using non-reduced/reduced 2-dimensional electrophoresis (NR/R-2DE), we clearly demonstrated that E3-independent ubiquitination by Ube2K produced not only unanchored but also Ube2K-linked polyubiquitins through thioester and isopeptide bonds. E3-independent assembly of polyubiquitins on the catalytic cysteine of Ube2K strongly supports the possibility of ‘en bloc transfer’ for polyubiquitination. From the same analyses of E3-independent ubiquitination products by other E2s, we also found that different lengths of polyubiquitins were linked to different E2s through thioester bond; longer chains by Cdc34 like Ube2K, short chains by Ube2g2, and mono-ubiquitin by UbcH10. Our results suggest that E2s possess the different intrinsic catalytic activities for polyubiquitination. (... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464936 Fri, 11 Nov 2011 05:00:00 +0100 5464936 http://www.medworm.com/index.php?rid=5464924&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008283%2Fabstract%3Frss%3Dyes Highlights: ► We investigated the effect of F71L mutation in αA-crystallin.► Thermal stability of the protein was compromised due to F71L substitution.► The F71L-mutant has defective chaperone-like activity upon heat treatment.► F71L-mutant failed to protect the αB-subunit from heat-induced aggregation.► The F71L-mutation may cause cataract in synergy with other factors during aging.Abstract: Previously we identified a novel mutation (F71L) in the αA-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not sig... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464924 Fri, 11 Nov 2011 05:00:00 +0100 5464924 http://www.medworm.com/index.php?rid=5464947&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311008106%2Fabstract%3Frss%3Dyes In the original publication, two unfortunate errors occurred in Fig. 2B: (1) in the label on the x-axis, PI and PE should be interchanged; (2) the unit on the y-axis should read “μg/107 cells” instead of “μg/105 cells”. This applies to the unit on page 1987, line 11, left column and the units on page 1988, line 13 and 15, left column. The authors apology for any inconvenience caused. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464947 Thu, 10 Nov 2011 05:00:00 +0100 5464947 http://www.medworm.com/index.php?rid=5464931&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007861%2Fabstract%3Frss%3Dyes Highlights: ► Carbohydrate arrays were used to investigate RCA120 interaction with galactose. ► Sulfated galactose-containing probes were prepared from marine-derived galactans. ► RCA120 binding to galactose was enhanced by 2-O- or 6-O-sulfation. ► RCA120 binding to galactose was abolished by 4-O-sulfation. ► Erythrina cristagalli lectin cannot accommodate any sulfation on terminal galactose.Abstract: Lectins are used extensively as research tools to detect and target specific oligosaccharide sequences. Ricinus communis agglutinin I (RCA120) recognizes non-reducing terminal β-d-galactose (Galβ) and its specificities of interactions with neutral and sialylated oligosaccharides have been well documented. Here we use carbohydrate arrays of sulfated Galβ-containing oligosaccharide... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464931 Thu, 10 Nov 2011 05:00:00 +0100 5464931 http://www.medworm.com/index.php?rid=5374721&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100768X%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374721 Fri, 04 Nov 2011 04:00:00 +0100 5374721 http://www.medworm.com/index.php?rid=5464930&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100785X%2Fabstract%3Frss%3Dyes Highlights: ► New putative NtcA boxes identified in mcy promoters (Microcystis aeruginosa PCC7806). ► 2-oxoglutartate increased the affinity of NtcA for the mcyA promoter region. ► Data suggest that NtcA acts in this case as a repressor of microcystin synthesis. ► Data suggest that microcystin synthesis is regulated responding to the C/N balance.Abstract: The binding affinity of NtcA towards promoter regions of the microcystin gene cluster from Microcystis aeruginosa PCC 7806 has been analyzed by band-shift assay (EMSA). The key nitrogen transcriptional regulator exhibits affinity for two fragments of the bidirectional mcyDA promoter, as well as for promoter regions of mcyE and mcyH. The presence of 2-oxoglutarate increased by 2.5 fold the affinity of NtcA for the mcyA promoter reg... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464930 Thu, 03 Nov 2011 04:00:00 +0100 5464930 http://www.medworm.com/index.php?rid=5464923&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007976%2Fabstract%3Frss%3Dyes Highlights: ► We have analyzed the substrate kinetics of the GTPase activity of FtsZ. ► We have studied the effect of GDP and the GTP analogue GMPCPP on the GTPase activity. ► The GTPase activity follows Michaelis–Menten kinetics. ► GDP and GMPCPP inhibited the activity in a competitive manner. ► We conclude that the GTPase active sites in FtsZ filaments are independent.Abstract: We have analyzed the substrate kinetics of the GTPase activity of FtsZ and the effects of two different GTPase inhibitors, GDP and the slowly hydrolyzable GTP analogue GMPCPP. In the absence of inhibitors the GTPase activity follows simple Michaelis–Menten kinetics, and both GDP and GMPCPP inhibited the activity in a competitive manner. These results indicate that the GTPase active sites in FtsZ fila... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464923 Thu, 03 Nov 2011 04:00:00 +0100 5464923 http://www.medworm.com/index.php?rid=5464922&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007964%2Fabstract%3Frss%3Dyes Highlights: ► PTIP BRCT5/6 domains have a high binding affinity for the γH2AX tail. ► We determine the crystal structure of BRCT5/6–γH2AX tail complex at 2.15Å resolution. ► Our study provides new clues to identify the role of PTIP in DDR pathways.Abstract: Human Pax2 transactivation domain-interacting protein (hPTIP), containing six BRCT domains, is an essential protein required for the IR induced DDR process with an unclear role. Here we report that the tandem BRCT5–BRCT6 domain of hPTIP recognizes the γH2AX tail, and this interaction depends on the phosphorylation of H2AX Ser139 and binding with the carboxyl ending peptide to the aminoacyl ending peptide. The 2.15Å crystal structure of hPTIP BRCT5/6–γH2AX complex and mutation analysis provide molecular evidence for dir... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464922 Thu, 03 Nov 2011 04:00:00 +0100 5464922 http://www.medworm.com/index.php?rid=5464921&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007940%2Fabstract%3Frss%3Dyes We describe the heterologous expression of the GTP-binding domain of septin 7. ► Crystals of the purified protein were obtained. ► The GTP-binding domains form filaments within the crystal lattice. ► These employ identical interfaces to those described for the hetero-filament of septins 2, 6 and 7. ► We discuss the implications for filament assembly.Abstract: We describe the purification, crystallization and structure for the GTP-binding domain of human septin 7 (SEPT7G). We show that it forms filaments within the crystal lattice which employ both the G and NC interfaces, similar to those seen in the hetero-filament of SEPT2/6/7. The NC interface is considered promiscuous as it is absent from the hetero-filament. Such promiscuity could provide the potential for permuting monomers a... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464921 Thu, 03 Nov 2011 04:00:00 +0100 5464921 http://www.medworm.com/index.php?rid=5464934&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007927%2Fabstract%3Frss%3Dyes We report the presence of an unexpected extra loop in the structure of Bacillus anthracis NAT1 enzyme. ► The extra loop may contribute to the shape of the active-site and to cofactor binding. ► Endogenous CoA cocrystallized with B. anthracis NAT1. ► We discuss the divergence in the mode of binding and location of CoA in NAT enzymes.Abstract: Arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that biotransform arylamine drugs. The Bacillus anthracis (BACAN)NAT1 enzyme affords increased resistance to the antibiotic sulfamethoxazole through its acetylation. We report the structure of (BACAN)NAT1. Unexpectedly, endogenous coenzymeA was present in the active site. The structure suggests that, contrary to the other prokaryotic NATs, (BACAN)NAT1 possesses a 14-residue... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464934 Wed, 02 Nov 2011 04:00:00 +0100 5464934 http://www.medworm.com/index.php?rid=5464933&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007915%2Fabstract%3Frss%3Dyes We report that 6-TG is also readily incorporated into mitochondrial DNA (mtDNA) where it is rapidly oxidized. The oxidized forms of mtDNA 6-TG inhibit replication by DNA Pol-γ. Accumulation of oxidized 6-TG is associated with reduced mtDNA transcription, a decline in mitochondrial protein levels, and loss of mitochondrial function. Ultraviolet A radiation (UVA) also oxidizes mtDNA 6-TG. Cells without mtDNA are less sensitive to killing by a combination of 6-TG and UVA than their mtDNA-containing counterparts, indicating that photochemical mtDNA 6-TG oxidation contributes to 6-TG-mediated UVA photosensitization. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464933 Wed, 02 Nov 2011 04:00:00 +0100 5464933 http://www.medworm.com/index.php?rid=5464932&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007903%2Fabstract%3Frss%3Dyes Highlights: ► First characterization of EF-hand containing Ca2+-binding MCF proteins. ► Phylogeny indicates two functionally unrelated sub-families. ► Unknown carrier of the SAMTL family at chloroplasts as potential SAM transporter. ► Three carriers at mitochondria are likely Ca2+-regulated ATP-Mg/Pi transporters.Abstract: Chloroplasts and mitochondria are central to crucial cellular processes in plants and contribute to a whole range of metabolic pathways. The use of calcium ions as a secondary messenger in and around organelles is increasingly appreciated as an important mediator of plant cell signaling, enabling plants to develop or to acclimatize to changing environmental conditions. Here, we have studied the four calcium-dependent mitochondrial carriers that are encoded in the... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464932 Wed, 02 Nov 2011 04:00:00 +0100 5464932 http://www.medworm.com/index.php?rid=5464920&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007939%2Fabstract%3Frss%3Dyes Highlights: ► We have structurally and functionally characterized Helicobacter pylori DsbG. ► The monomeric and dimeric structures of H. pylori DsbG show significant differences compared to E. coli DsbG. ► H. pylori DsbG shows a reductase activity against HP0518, a putative l,d-transpeptidase in H. pylori.Abstract: Dsb proteins play important roles in bacterial pathogenicity. To better understand the role of Dsb proteins in Helicobacter pylori, we have structurally and functionally characterized H. pylori DsbG (HP0231). The monomer consists of two domains connected by a helical linker. Two monomers associate to form a V-shaped dimer. The monomeric and dimeric structures of H. pylori DsbG show significant differences compared to Escherichia coli DsbG. Two polyethylene glycol molecules... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464920 Wed, 02 Nov 2011 04:00:00 +0100 5464920 http://www.medworm.com/index.php?rid=5464919&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007897%2Fabstract%3Frss%3Dyes Highlights: ► Gid9 is a second subunit of the Gid ubiquitin ligase complex containing a degenerated RING finger domain. ► It forms a dimer with the ubiquitin ligase confering RING finger subunit Gid2. ► Also the RING finger of Gid9 is required for ubiquitin ligase activity in vivo.Abstract: The two major antagonistic pathways of carbon metabolism in cells, glycolysis and gluconeogenesis, are tightly regulated. In the eukaryotic model organism Saccharomyces cerevisiae the switch from gluconeogenesis to glycolysis is brought about by proteasomal degradation of the gluconeogenic enzyme fructose-1,6-bisphosphatase. The ubiquitin ligase responsible for polyubiquitylation of fructose-1,6-bisphosphatase is the Gid complex. This complex consists of seven subunits of which subunit Gid2/Rmd5 c... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464919 Mon, 31 Oct 2011 04:00:00 +0100 5464919 http://www.medworm.com/index.php?rid=5396439&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007885%2Fabstract%3Frss%3Dyes In this study, we found that Akt phosphorylates BLT2 at its C-terminal Thr355 residue and that this event is critical for BLT2-mediated chemotactic responses. In addition, we found that Rac1 stimulation and subsequent reactive oxygen species (ROS) production lie downstream of BLT2 phosphorylation, thus mediating chemotaxis.Structured summary of protein interactions: BLT2physically interacts with Akt by pull down (View interaction)BLT2physically interacts with Akt by pull down (View interaction) (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396439 Mon, 31 Oct 2011 04:00:00 +0100 5396439 http://www.medworm.com/index.php?rid=5464929&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007836%2Fabstract%3Frss%3Dyes Highlights: ► Saccharomyces cerevisiae RasGEF Cdc25 is localized in the nucleus, ER and plasma membrane. ► PKA activity drives Cdc25 to the cytosol. ► Ser825 and Ser826 mutation to Glu impairs Cdc25 localization to the nucleus.Abstract: In Saccharomyces cerevisiae the Cdc25/Ras/cAMP pathway is involved in cell growth and proliferation regulation. Ras proteins are regulated by Ira1/2 GTPase activating proteins (GAPs) and Cdc25/Sdc25 guanine nucleotide exchange factors (GEFs).Most of cytosolic Cdc25 protein was found on internal membranes in exponentially growing cells, while upon incubation in a buffer with no nutrients it is re-localized to plasma membrane. The overexpression of Tpk1 PKA catalytic subunit also induces Cdc25 export from the nucleus, involving two serine residues near ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464929 Wed, 26 Oct 2011 04:00:00 +0100 5464929 http://www.medworm.com/index.php?rid=5464918&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007848%2Fabstract%3Frss%3Dyes Highlights: ► Fission yeast MCMMCM–BP complex comprises Mcb1 and the Mcm3–Mcm7 proteins. ► Mcm2 is not a component of the MCMMCM–BP complex. ► Mcb1 inactivation leads to accumulation of Rad22 DNA repair foci. ► Mcb1 inactivation leads to Chk1-dependent checkpoint activation and cell cycle arrest. ► Mcb1 is required for successful meiosis.Abstract: The MCM (mini-chromosome maintenance) complex is the core of the eukaryotic replicative helicase and comprises six proteins, Mcm2–Mcm7. In humans, a variant form of the complex has Mcm2 replaced by the MCM–BP protein. Recent results suggest that a similar complex exists in fission yeast with an essential role in DNA replication and cell cycle progression. Here, we describe the purification and subunit composition of the fissio... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464918 Wed, 26 Oct 2011 04:00:00 +0100 5464918 http://www.medworm.com/index.php?rid=5464917&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007873%2Fabstract%3Frss%3Dyes Abstract: Plant hemoglobins constitute a diverse group of hemeproteins and evolutionarily belong to three different classes. Class 1 hemoglobins possess an extremely high affinity to oxygen and their main function consists in scavenging of nitric oxide (NO) at very low oxygen levels. Class 2 hemoglobins have a lower oxygen affinity and they facilitate oxygen supply to developing tissues. Symbiotic hemoglobins in nodules have mostly evolved from class 2 hemoglobins. Class 3 hemoglobins are truncated and represent a clade with a very low similarity to class 1 and 2 hemoglobins. They may regulate oxygen delivery at high O2 concentrations. Depending on their physical properties, hemoglobins belong either to hexacoordinate non-symbiotic or pentacoordinate symbiotic groups. Plant hemoglobins are... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464917 Wed, 26 Oct 2011 04:00:00 +0100 5464917 http://www.medworm.com/index.php?rid=5437088&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007824%2Fabstract%3Frss%3Dyes Abstract: Wiskott–Aldrich Syndrome (WAS) is a X-linked primary immunodeficiency disorder also marked by a very high (up to 70%) incidence of autoimmunity. Wiskott–Aldrich Syndrome arises from mutations in the Wiskott–Aldrich Syndrome protein (WASp), a cytoplasmic protein that links signaling by cell surface receptors such as the T-cell receptor and integrins to actin polymerization. WASp promotes the functions of multiple cell types that support immune responses, but also is important for the function of regulatory T cells and in TCR-induced apoptosis, two negative mechanisms of immune regulation that maintain peripheral immune tolerance. Here we review the nature of immune defects and autoimmunity in WAS and WASp deficient mice and discuss how this single gene defect can simultaneou... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5437088 Wed, 26 Oct 2011 04:00:00 +0100 5437088 http://www.medworm.com/index.php?rid=5464928&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007800%2Fabstract%3Frss%3Dyes Highlights: ► We examine the reported toxicity of TAP tagging proteins. ► TAP tagging does not generally cause loss of protein function. ► The MX marker cassettes are toxic to yeast at high copy numbers. ► Toxicity is due to the high copy presence of the heterologous TEF1 promoter. ► Genomic single copy integration of the MX marker and TEF1 promoter is not toxic.Abstract: Protein overexpression based on introduction of multiple gene copies is well established. To improve purification or quantification, proteins are typically fused to peptide tags. In Saccharomyces cerevisiae, this has been hampered by multicopy toxicity of the TAP and GFP cassettes used in the global strain collections. Here, we show that this effect is due to the EF-1α promoter in the HIS3MX marker cassette rat... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5464928 Mon, 24 Oct 2011 04:00:00 +0100 5464928 http://www.medworm.com/index.php?rid=5437079&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007770%2Fabstract%3Frss%3Dyes Abstract: A hypomorphic mutation of the gene encoding zeta-associated protein-70 (ZAP-70), a signaling molecule in T cells, produces autoimmune arthritis in mice under a microbially conventional condition but not in a clean environment. The genetic anomaly alters thymic selection of self-reactive T cells as well as natural regulatory T cells and their respective functions. Highly self-reactive polyclonal T cells, including arthritogenic ones, thus produced by the thymus strongly recognize self-antigens presented by antigen-presenting cells, stimulate them to up-regulate co-stimulatory molecules and secrete cytokines that drive naïve self-reactive T cells to differentiate into autoimmune effector Th17 cells. Administration of microbial products and activation of complement can facilitate t... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5437079 Mon, 24 Oct 2011 04:00:00 +0100 5437079 http://www.medworm.com/index.php?rid=5437074&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007812%2Fabstract%3Frss%3Dyes Based on their severity and chronicity, rheumatoid arthritis (RA) and multiple sclerosis (MS) are the most disabling autoimmune diseases in humans. However, RA and MS also represent excellent examples to understand the communication between the central nervous system (CNS) and the immune system. In RA, breach in immune tolerance results in peripheral autoimmune disease, which in consequence profoundly affects the CNS via neuroimmune mechanisms . On the other hand, breach in immune tolerance in MS directly leads to inflammation in the CNS, which then results in the dysfunction of peripheral organs. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5437074 Mon, 24 Oct 2011 04:00:00 +0100 5437074 http://www.medworm.com/index.php?rid=5396454&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007794%2Fabstract%3Frss%3Dyes Highlights: ► Two new crystals structures of the wild type EphA4 kinase domain (KD) are presented. ► The apo-EphA4 KD structure contains an unknown hydrophobic back-pocket in the ATP-binding site. ► Dasatinib-EphA4 KD structure revealed a binding mode similar to the one seen in Src family members.Abstract: The Eph family of receptor tyrosine kinases regulates diverse cellular processes while the over-expression of a member of this family, EphA4, has been reported in a variety of malignant carcinomas. To gain insight into molecular mechanisms and to facilitate structure-based inhibitor design, we solved the crystal structure of the native EphA4 kinase domain in both the apo and dasatinib bound forms. Analysis of the two structures provides insight into structural features of inhibitor... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396454 Mon, 24 Oct 2011 04:00:00 +0100 5396454 http://www.medworm.com/index.php?rid=5396453&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007782%2Fabstract%3Frss%3Dyes Highlights: ► We used an opsin structure as template for a homology model of an active GPCR. ► By MD simulations, we determined dynamic interaction fingerprints between receptor model and ligands. ► Agonist fingerprints selectively found agonists in a ligand test set. ► Our technique can be used to discriminate agonists and antagonists/inverse agonists in virtual ligand libraries.Abstract: Most of the currently available G protein-coupled receptor (GPCR) crystal structures represent an inactive receptor state, which has been considered to be suitable only for the discovery of antagonists and inverse agonists in structure-based computational ligand screening. Using the β2-adrenergic receptor (B2AR) as a model system, we show that a dynamic homology model based on an “active” op... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396453 Mon, 24 Oct 2011 04:00:00 +0100 5396453 http://www.medworm.com/index.php?rid=5396449&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007617%2Fabstract%3Frss%3Dyes Highlights: ► We have shown differential miRNA expression profiles between SW1116/HCPT and SW1116. ► Overexpression of miR-506 confers resistance to HCPT in SW1116. ► PPARα is a common target of miR-506. ► Cytotoxic ability of HCPT requires the concomitant presence of PPARα.Abstract: Chemotherapeutic drug resistance remains a major obstacle to the successful treatment of colon cancer. Here, we show that 77 differentially expressed miRNAs were identified in SW1116/HCPT versus SW1116, and over-expressed miR-506 in SW1116/HCPT cells was validated. Then it was indicated that PPARα is a common target of miR-506 by using a luciferase reporter assay. Our results also demonstrated that cytotoxic ability of HCPT requires the concomitant presence of PPARα, and that loss of PPARα express... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396449 Mon, 24 Oct 2011 04:00:00 +0100 5396449 http://www.medworm.com/index.php?rid=5396452&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007654%2Fabstract%3Frss%3Dyes Highlights: ► Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis. ► miR-124 may suppress the expression of AHR by targeting its 3′-UTR. ► Targeting of miR-124 opens new therapeutic avenues in neuroblastoma.Abstract: Neuroblastoma is the most common extracranial solid tumor in children. We investigate whether miR-124, the abundant neuronal miRNA, plays a pivotal role in neuroblastoma. Knockdown of miR-124 promotes neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis. Further miR-124 is predicted to target aryl hydrocarbon receptor (AHR) which may promote neuroblastoma cell differentiation. We validate that miR-124 may suppress the expression of AHR by targeting its 3′-UTR. These results suggest that miR-1... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396452 Fri, 21 Oct 2011 04:00:00 +0100 5396452 http://www.medworm.com/index.php?rid=5396451&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007642%2Fabstract%3Frss%3Dyes Highlights: ► Two isoforms of IκBL were identified in mouse cells. ► IκBL showed suppressive effects on NF-κB and inflammatory cytokine expressions. ► IκBL’s nuclear localization signal and ankyrin repeat were required for the activity. ► NFκB activation cascade in the cytoplasm was not influenced by IκBL. ► These findings suggested that IκBL is a novel member of the nuclear IκB.Abstract: We previously reported that IκBL prevents experimental autoimmune arthritis. The molecular mechanism, however, still remains unclear. In contrast to four splicing-isoforms of IκBL in human, two isoforms were identified in mouse. The major isoform IκBL-α(S) suppressed LPS-induced NF-κB activation and transcription of TNFα and IL-6, but not IL-1β. The suppressive activity required... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396451 Fri, 21 Oct 2011 04:00:00 +0100 5396451 http://www.medworm.com/index.php?rid=5396450&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007629%2Fabstract%3Frss%3Dyes Highlights: ► Aurora-B levels decreased during replicative senescence and premature senescence. ► Aurora-B overexpression in old cells partially reversed senescence phenotypes. ► In contrast, Aurora-B down-regulation accelerated cellular senescence. ► p53 knockdown but not p16 knockdown inhibited cell senescence by Aurora-B down-regulation. ► Aurora-B may regulate cellular senescence of human primary cells via a p53 pathway.Abstract: Aurora B kinase (Aurora-B) functions in chromosome segregation and cleavage of polar spindle microtubules. However, its role in cellular senescence remains elusive. Here, we investigated Aurora-B effects on cellular senescence in human fibroblasts and endothelial cells. Aurora-B levels were reduced during replicative senescence and premature senescen... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396450 Fri, 21 Oct 2011 04:00:00 +0100 5396450 http://www.medworm.com/index.php?rid=5396442&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007538%2Fabstract%3Frss%3Dyes We describe the crystal structures of GTP and GDP forms of Ypt32 to understand the molecular basis for Rab function. The structure of Ypt32(GTP) reveals that the switch II conformation is distinct from Sec4(GTP) in spite of a highly conserved amino acid sequence. Also, Ypt32(GDP) reveals a remarkable change in conformation of the switch II helix induced by binding to GDI, which has not been described previously. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396442 Fri, 21 Oct 2011 04:00:00 +0100 5396442 http://www.medworm.com/index.php?rid=5396443&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100754X%2Fabstract%3Frss%3Dyes We describe purification schemes to obtain DHFR samples with only desired ligands.Abstract: Dihydrofolate reductase (DHFR) is a well-studied drug target and a paradigm for understanding enzyme catalysis. Preparation of pure DHFR samples, in defined ligand-bound states, is a prerequisite for in vitro studies and drug discovery efforts. We use NMR spectroscopy to monitor ligand content of human and Escherichia coli DHFR (ecDHFR), which bind different co-purifying ligands during expression in bacteria. An alternate purification strategy yields highly pure DHFR complexes, containing only the desired ligands, in the quantities required for structural studies. Interestingly, ecDHFR is bound to endogenous THF while human DHFR is bound to NADP. Consistent with these findings, a designed “humaniz... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396443 Thu, 20 Oct 2011 04:00:00 +0100 5396443 http://www.medworm.com/index.php?rid=5396455&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007526%2Fabstract%3Frss%3Dyes The sentence that reads “In cc6A and cc6B, Lys241 corresponds to Asp1440” in paragraph 3.3. Inhibition studies on cc4C and cc6A, should instead read “In cc6A and cc6B, Lys241 corresponds to a glycine (Gly1435 in KDM6B and Gly1191 in KDM6A). (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396455 Wed, 19 Oct 2011 04:00:00 +0100 5396455 http://www.medworm.com/index.php?rid=5396448&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007605%2Fabstract%3Frss%3Dyes Highlights: ► Diabetogenic L213R in SUR1 L0 hyperactivates KATP by destabilizing its closed state. ► This kinetic mechanism attenuates KATP inhibition by ATP and sulfonylureas. ► Our analysis reveals a key role for L0 helix in controlling KATP gating.Abstract: Activating mutations in different domains of the ABCC8 gene-coded sulfonylurea receptor 1 (SUR1) cause neonatal diabetes. Here we show that a diabetogenic mutation in an unexplored helix preceding the ABC core of SUR1 dramatically increases open probability of (SUR1/Kir6.2)4 channel (KATP) by reciprocally changing rates of its transitions to and from the long-lived, inhibitory ligand-stabilized closed state. This kinetic mechanism attenuates ATP and sulfonylurea inhibition, but not Mg-nucleotide stimulation, of SUR1/Kir6.2. The... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396448 Wed, 19 Oct 2011 04:00:00 +0100 5396448 http://www.medworm.com/index.php?rid=5396447&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007587%2Fabstract%3Frss%3Dyes Highlights: ► Chaetocin, an inhibitor of the Suv39H1 methyltransferase, causes induction of latent HIV-1. ► Treatment with chaetocin does not cause a global T cell response. ► Chaetocin produces minimal toxicity at concentrations necessary for peak induction. ► HDAC inhibitors in combination with chaetocin cause a synergistic response of HIV-1 expression.Abstract: Latent HIV-1 (human immunodeficiency virus-1) provirus is unaffected by current AIDS (acquired immunodeficiency syndrome) therapies. We show here that chaetocin, an SUV39H1 histone methyltransferase inhibitor, causes 25-fold induction of latent HIV-1 expression, while producing minimal toxicity and without causing T cell activation. Induction is associated with loss of histone H3 lysine 9 (H3K9) trimethylation at the long... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396447 Wed, 19 Oct 2011 04:00:00 +0100 5396447 http://www.medworm.com/index.php?rid=5396446&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007575%2Fabstract%3Frss%3Dyes Highlights: ► We studied the role of CD38 in formation of the second messenger NAADP. ► We used gene silencing and CD38 KO mice to show a lack of inhibition of NAADP synthesis. ► We conclude that CD38 appears to be a NAADP degrading enzyme in intact cells.Abstract: The role of the multifunctional enzyme CD38 in formation of the Ca2+-mobilizing second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) was investigated. Gene silencing of CD38 did neither inhibit NAADP synthesis in intact Jurkat T cells nor in thymus or spleen obtained from CD38 knock out mice. In vitro, both NAADP formation by base-exchange and degradation to 2-phospho adenosine diphosphoribose were efficiently decreased. Thus in vivo CD38 appears to be a NAADP degrading rather than a NAADP forming enzyme,... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396446 Wed, 19 Oct 2011 04:00:00 +0100 5396446 http://www.medworm.com/index.php?rid=5396445&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007563%2Fabstract%3Frss%3Dyes Highlights: ► A prokaryotic enzyme (Maqu_2220) is shown to reduce fatty acyl-CoA to fatty alcohol. ► Maqu_2220 can utilize a broad range of acyl-CoA as substrates. ► Maqu_2220 can utilize ACP bound acyl chain as substrate. ► Homologous sequences to Maqu_2220 are found in a narrow range of prokaryotic genera. ► Amino acid sequences homologous to Maqu_2220 are found widely among eukaryotes.Abstract: The reduction of acyl-CoA or acyl-ACP to fatty alcohol occurs via a fatty aldehyde intermediate. In prokaryotes this reaction is thought to be performed by separate enzymes for each reduction step while in eukaryotes these reactions are performed by a single enzyme without the release of the intermediate fatty aldehyde. However, here we report that a purified fatty acyl reductase from M... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396445 Wed, 19 Oct 2011 04:00:00 +0100 5396445 http://www.medworm.com/index.php?rid=5396444&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007551%2Fabstract%3Frss%3Dyes Highlights: ► MsbA is a cell transporter with ATPase and transmembrane domains separated by ∼50Å. ► MsbA was successfully reconstituted in nanodiscs in a functional state. ► Catalytic domain is sensitive to physical properties of bilayer. ► ATPase and transmembrane domains are physically distant, but functionally linked.Abstract: ATP-binding cassette (ABC) transporters couple hydrolysis of ATP with vectorial transport across the cell membrane. We have reconstituted ABC transporter MsbA in nanodiscs of various sizes and lipid compositions to test whether ATPase activity is modulated by the properties of the bilayer. ATP hydrolysis rates, Michaelis–Menten parameters, and dissociation constants of substrate analog ATP-γ-S demonstrated that physicochemical properties of the bilay... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396444 Wed, 19 Oct 2011 04:00:00 +0100 5396444 http://www.medworm.com/index.php?rid=5374745&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007514%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374745 Tue, 18 Oct 2011 04:00:00 +0100 5374745 http://www.medworm.com/index.php?rid=5396440&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007381%2Fabstract%3Frss%3Dyes Highlights: ► We investigated the integrative role of kinins in mosquito blood feeding adaptation. ► The head, ovaries, posterior midgut and hindgut express the kinin receptor protein. ► Midgut endocrine cells and rectal papillae show receptor immunostaining. ► Receptor partial silencing was achieved in Malpighian tubules and rectum by RNAi. ► RNAi reduced fluid excretion in vivo by 50% during post-peak diuresis.Abstract: The evolution of the blood feeding adaptation in mosquitoes required hormonal coordination of multiple physiological processes (behavior, digestion, diuresis, oogenesis). The Aedes kinins (leucokinin-like neuropeptides) are involved in post blood feeding physiological processes, having diuretic and myotropic functions. To understand the in vivo contribution of t... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396440 Mon, 17 Oct 2011 04:00:00 +0100 5396440 http://www.medworm.com/index.php?rid=5310475&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007216%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310475 Thu, 13 Oct 2011 08:15:44 +0100 5310475 http://www.medworm.com/index.php?rid=5396441&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007447%2Fabstract%3Frss%3Dyes Highlights: ► The conformation and orientation of α-synuclein on membrane depend on bilayer properties. ► The binding to the lipid bilayer does not require complete formation of an α-helical region. ► At low lipid/protein ratio α-synuclein interacts with membranes primarily through its N-terminus.Abstract: Interactions of the presynaptic protein α-synuclein with membranes are involved in its physiological action as well as in the pathological misfolding and aggregation related to Parkinsons’s disease. We studied the conformation and orientation of α-synuclein bound to model vesicular membranes using multiparametric response polarity-sensitive fluorescent probes together with CD and EPR measurements. At low lipid to α-synuclein ratio the protein binds membranes through its N-t... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5396441 Thu, 13 Oct 2011 04:00:00 +0100 5396441 http://www.medworm.com/index.php?rid=5374725&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007137%2Fabstract%3Frss%3Dyes Highlights: ► Thr-128 and Tyr-146 in RT are responsible for protease-mediated Gag–Pol processing. ► Substitution of Thr-128 and Tyr-146 with Ala impaired RT dimerization. ► RT dimerization may affect Gag–Pol processing.Abstract: The efficient processing of human immunodeficiency virus type 1 Gag–Pol requires not only protease activity but also specific reverse transcriptase (RT) and integrase sequences. However, the critical amino acid residues of the HIV-1 Pol gene involved in protease-mediated Gag–Pol processing have not been precisely defined. Here, we found that the substitution of Thr-128 or Tyr-146 with Ala markedly impaired the proteolytic processing of the MA/CA, p66/p51 and RT/IN sites but did not affect the normal processing of other sites. Moreover, a Thr-128 or Ty... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374725 Thu, 13 Oct 2011 04:00:00 +0100 5374725 http://www.medworm.com/index.php?rid=5374744&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007472%2Fabstract%3Frss%3Dyes Highlights: ► We analyzed the effect of Ca2+-calmodulin on membrane integration of tail-anchored proteins. ► We found that Ca2+-calmodulin inhibits membrane insertion of TA proteins. ► This inhibition was prevented by trifluoperazine, a CaM antagonist. ► The effect of Ca2+-CaM was also seen for a purified TA protein. Ca2+-CaM can be cross-linked to TA proteins.Abstract: Cytosolic components and pathways have been identified that are involved in inserting tail-anchored (TA) membrane proteins into the yeast or mammalian endoplasmic reticulum (ER) membrane. Searching for regulatory mechanisms of TA protein biogenesis, we found that Ca2+-calmodulin (CaM) inhibits the insertion of TA proteins into mammalian ER membranes and that this inhibition is prevented by trifluoperazine, a CaM ant... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374744 Wed, 12 Oct 2011 04:00:00 +0100 5374744 http://www.medworm.com/index.php?rid=5374739&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007393%2Fabstract%3Frss%3Dyes Highlights: ► Staphylococcal γ-hemolysin membrane pores form clusters on erythrocyte membranes. ► Membranes around clusters disappear and large holes are formed. ► Single pore formation correlates with the release of K+ ions from erythrocytes. ► Cluster formation correlates with the release of hemoglobin from erythrocytes. ► The clustered pores increase with the increase of the number of clusters per cell.Abstract: Staphylococcal γ-hemolysin (Hlg) is a pore-forming toxin consisting of two separate components, LukF (34kDa) and Hlg2 (32kDa). Here we show that Hlg pores aggregate and form clusters on human erythrocyte membranes in association with increasing hemolytic activity. Quantitative analysis using transmission electron microscopy and image processing revealed that the form... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374739 Wed, 12 Oct 2011 04:00:00 +0100 5374739 http://www.medworm.com/index.php?rid=5374730&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007484%2Fabstract%3Frss%3Dyes Highlights: ► Hepatic menin expression is downregulated in fatty liver models. ► Liver specific menin deficiency promotes hepatic steatosis. ► Restoration of hepatic menin in db/db mice prevents liver steatosis. ► Menin cooperates with nuclear receptor PPARα.Abstract: Fatty liver is strongly associated with metabolic syndrome. Here, we show that the impaired hepatic expression of menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, represents a common feature of several fatty liver mouse models. The liver specific ablation of MEN1 gene expression in healthy mice induced hepatic steatosis under high-fat dietary conditions. Moreover, overexpression of menin in livers of steatotic db/db mice reduced liver triglyceride accumulation. At the molecu... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374730 Wed, 12 Oct 2011 04:00:00 +0100 5374730 http://www.medworm.com/index.php?rid=5374729&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007460%2Fabstract%3Frss%3Dyes In this study, we report that AgsA, a sHsp of Salmonella enterica serovar Typhimurium, spontaneously forms fibrils in vitro. These fibrils tend to be formed at elevated temperature and do not share the characteristics of amyloid. Interestingly, the fibril-forming AgsA is able to suppress the dithiothreitol-induced aggregation of insulin efficiently within a certain range of temperature. During this process, AgsA fibrils disappear and spherical complexes form between AgsA and insulin molecules. These data suggest that AgsA fibrils may represent a distinctive type of structural and functional form of sHsp from spherical oligomers. Our study provides new insights into sHsp structures and chaperone functions.Structured summary of protein interactions: AgsA and AgsA bind by electron microscopy ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374729 Wed, 12 Oct 2011 04:00:00 +0100 5374729 http://www.medworm.com/index.php?rid=5374743&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007459%2Fabstract%3Frss%3Dyes Highlights: ► The ligand-type specificity of MHC I proteins (P, L, N) cannot be distinguished on the sequence space. ► SVM and kNN classifiers predict the ligand-type specificity of MHC I proteins with great accuracy. ► The ligand-type specificity of various uncharacterized MHC Ib proteins has been predicted.Abstract: Functional characterization of proteins belonging to the MHC I superfamily involves knowing their cognate ligands, which can be peptides, lipids or none. However, the experimental identification of these ligands is not an easy task and generally requires some a priori knowledge of their chemical nature (ligand-type specificity). Here, we trained k-nearest neighbor and support vector machine classifiers that predict the ligand-type specificity MHC I proteins with great a... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374743 Tue, 11 Oct 2011 04:00:00 +0100 5374743 http://www.medworm.com/index.php?rid=5374742&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007435%2Fabstract%3Frss%3Dyes Highlights: ► We compared protein splicing between 20 different inteins in three identical foreign extein contexts. ► Effects of exteins and temperature were compared for the 20 inteins. ► Pho RadA intein and Npu DnaB mini-intein were discovered to have high splicing efficiency.Abstract: Protein splicing catalyzed by inteins has enabled various biotechnological applications such as protein ligation. Successful applications of inteins are often limited by splicing efficiency. Here, we report the comparison of protein splicing between 20 different inteins from various organisms in identical contexts to identify robust inteins with foreign exteins. We found that RadA intein from Pyrococcus horikoshii and an engineered DnaB intein from Nostoc punctiforme demonstrated an equally efficient... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374742 Tue, 11 Oct 2011 04:00:00 +0100 5374742 http://www.medworm.com/index.php?rid=5374741&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007423%2Fabstract%3Frss%3Dyes Highlights: ► Protease inhibitor, PMSF mediated peptide re-synthesis. ► Fast religation of peptides in the presence of a small molecule. ► X-ray structure of a nicked protein.Abstract: Protease inhibitors have been extensively used in research to prevent unwanted degradation of proteins during purification and analysis. Here, we report a remarkable discovery of protease inhibitor mediated reformation of peptide bonds by the serine protease inhibitor, PMSF in a diverse set of proteolyzed molecules. Interestingly, the religation reaction in the presence of PMSF occurs in a very short time period and with very high yields of the religated product. We also investigate the plausible mechanism of such a reaction and demonstrate through biochemical studies and X-ray crystallography that pro... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374741 Tue, 11 Oct 2011 04:00:00 +0100 5374741 http://www.medworm.com/index.php?rid=5374740&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100740X%2Fabstract%3Frss%3Dyes Highlights: ► We found a novel anti-inflammatory peptide (GC31) from human thrombomodulin. ► GC31 peptide suppressed the development of endotoxin induced uveitis. ► GC31 decreased leukocyte counts and protein concentration in aqueous humor. ► GC31 inhibited LPS-induced TNF-α, IL-6 and MCP-1 expression in vivo and in vitro. ► GC31 interrupted LPS-induced NF-κB activation in vitro.Abstract: Thrombomodulin (TM) is a single-transmembrane glycoprotein receptor for thrombin, which is best known as a cofactor for thrombin-mediated activation of anticoagulant protein C. C-type lectin-like domain (CTLD) of TM has distinct coagulation/fibrinolysis-independent anti-inflammatory properties. Here we found anti-inflammatory effects of a novel peptide (GC31) from CTLD of TM in endotoxin-induc... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374740 Tue, 11 Oct 2011 04:00:00 +0100 5374740 http://www.medworm.com/index.php?rid=5374731&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007496%2Fabstract%3Frss%3Dyes Highlights: ► The propeller loop of DPP-IV is required for its dimerization and activity. ► The same loop of DPP9 is required for its activity but not dimerization. ► It suggests differential structural and functional roles of the loop among DPPs.Abstract: The dipeptidyl peptidase (DPP) family members, including DPP-IV, DPP8, DPP9 and others, cleave the peptide bond after the penultimate proline residue and are drug target rich. The dimerization of DPP-IV is required for its activity. A propeller loop located at the dimer interface is highly conserved within the family. Here we carried out site-directed mutagenesis on the loop of DPPIV and identified several residues important for dimer formation and enzymatic activity. Interestingly, the corresponding residues on DPP9 have a differe... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374731 Tue, 11 Oct 2011 04:00:00 +0100 5374731 http://www.medworm.com/index.php?rid=5374728&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007411%2Fabstract%3Frss%3Dyes In this study, photoregulation of the kinase in phototropin1 (phot1) was studied using LOV2-linker-kinase polypeptide. We designed a new substrate consisting of the N-terminal part of the phot1 with autophosphorylation sites. The LOV2-linker-kinase had the same spectroscopic properties as those of the LOV2 core and phosphorylated the substrate in a light-dependent manner. Amino acid substitution experiments proved that the phosphorylation comes from the activation of the kinase via photoreaction of LOV2.Structured summary of protein interactions:AtPhot1-LOV2 phosphorylates AtPhot1-Nt by protein kinase assay (View Interaction: 1, 2, 3) (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374728 Tue, 11 Oct 2011 04:00:00 +0100 5374728 http://www.medworm.com/index.php?rid=5374727&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100737X%2Fabstract%3Frss%3Dyes Highlights: ► We demonstrate that DUSP-UBL double domain can exist in different oligomeric states. ► We solve structures of DUSP-UBL from USP15 monomer and dimer. ► We identify structural features that dictate the oligomeric state of DUSP-UBL unit and disposition of constituent domains. ► We analyze the physiological state of USP15.Abstract: USP4, 11 and 15 are three closely related paralogues of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. The DUSP domain and the UBL domain in these proteins are juxtaposed which may provide a functional unit conferring specificity. We determined the structures of the USP15 DUSP-UBL double domain unit in monomeric and dimeric states. We then conducted comparative analysis of the structural and physical properties of all... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374727 Tue, 11 Oct 2011 04:00:00 +0100 5374727 http://www.medworm.com/index.php?rid=5374736&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007149%2Fabstract%3Frss%3Dyes In this report, we show that Oct-1 acts as an activator of catalase, by binding to the catalase promoter in hepatocellular carcinoma (HCC) cell lines. In addition, we suggest that Oct-1 is downregulated by ROS via CpG island methylation in its promoter. These findings contribute to a better understanding of the epigenetic changes induced by ROS in the process of carcinogenesis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374736 Fri, 07 Oct 2011 04:00:00 +0100 5374736 http://www.medworm.com/index.php?rid=5374738&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007174%2Fabstract%3Frss%3Dyes Highlights: ► Characterization of closely related CYP71Z6 & 7 demonstrates different activity. ► Biochemical activity suggests distinct roles in rice diterpenoid metabolism. ► Results provide insight into plant biosynthetic gene cluster evolution.Abstract: Rice (Oryza sativa) contains a biosynthetic gene cluster associated with production of at least two groups of diterpenoid phytoalexins, the antifungal phytocassanes and antibacterial oryzalides. While cytochromes P450 (CYP) from this cluster are known to be involved in phytocassane production, such mono-oxygenase activity relevant to oryzalide biosynthesis was unknown. Here we report biochemical characterization demonstrating that CYP71Z6 from this cluster acts as an ent-isokaurene C2-hydroxylase that is presumably involved in the ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374738 Wed, 05 Oct 2011 04:00:00 +0100 5374738 http://www.medworm.com/index.php?rid=5374737&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007162%2Fabstract%3Frss%3Dyes In this study, we show that transcription of the gene for PacC is modulated in response to nutrient changes, phosphate and carbon sources, and pH. In addition, we show that transcription of pacC is modulated in response to alternative RNA splicing of the palB gene. These results reveal novel aspects of the complex network involved in modulation of pacC. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374737 Wed, 05 Oct 2011 04:00:00 +0100 5374737 http://www.medworm.com/index.php?rid=5374734&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007113%2Fabstract%3Frss%3Dyes Highlights: ► VCP levels are decreased in Alzheimer disease brain. ► VCP knockdown in neurons decreases total soluble tau levels. ► VCP knockdown increases the levels of tau phosphorylated at Ser262/356. ► Inhibition of autophagy increases soluble tau phosphorylated at Ser262/356.Abstract: VCP/p97 is a multifunctional AAA+-ATPase involved in vesicle fusion, proteasomal degradation, and autophagy. Reported dysfunctions of these processes in Alzheimer disease (AD), along with the linkage of VCP/p97 to inclusion body myopathy with Paget’s disease and frontotemporal dementia (IBMPFD) led us to examine the possible linkage of VCP to the AD-relevant protein, tau. VCP levels were reduced in AD brains, but not in the cerebral cortex of an AD mouse model, suggesting that VCP reduction occ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374734 Wed, 05 Oct 2011 04:00:00 +0100 5374734 http://www.medworm.com/index.php?rid=5374726&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007186%2Fabstract%3Frss%3Dyes Highlights: ► MT1-MMP inhibition induces fibronectin assembly in tumor cells. ► MT1-MMP expression in fibroblasts reduces fibronectin assembly. ► MT1-MMP degrades assembled fibronectin to promote cell motility. ► MT1-MMP inhibition generates a robust fibronectin assembly in collagen gel matrix, which restricts tumor cell invasion.Abstract: Fibronectin (FN) matrix assembly is an essential process in normal vertebrate development, which is frequently lost in tumor cells. Here we show that membrane-type 1 matrix metalloproteinase (MT1-MMP) regulates FN matrix assembly. MT1-MMP knockdown induced FN assembly in breast carcinoma cells. Ectopic expression of MT1-MMP reduced specifically the assembled FN matrix level without affecting whole FN production in fibroblasts. Treatment of fibros... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374726 Wed, 05 Oct 2011 04:00:00 +0100 5374726 http://www.medworm.com/index.php?rid=5374722&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311006764%2Fabstract%3Frss%3Dyes Highlights: ► RNA polymerase I (RNAPI) is one of three universally conserved transcription enzymes of eukaryotes. ► Its essential and conserved Rpa43 subunit was previously reported to act in transcript initiation. ► Large hydrophilic motifs of Rpa43 interact with subunits acting in RNA elongation (Rpa12, Rpa49). ► Rpa43 binds the elongation factor Spt5 and the histone chaperone Spt6 in 2-hybrid assay tests. ► Rpa43 may thus have a dual role in transcript initiation and promoter escape.Abstract: An Rpa43/Rpa14 stalk protrudes from RNA polymerase I (RNAPI), with homology to Rpb7/Rpb4 (RNAPII), Rpc25/Rpc17 (RNAPIII) and RpoE/RpoF (archaea). In fungi and vertebrates, Rpa43 contains hydrophilic domains forming about half of its size, but these domains lack in Schizosaccharomyces pomb... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374722 Tue, 04 Oct 2011 04:00:00 +0100 5374722 http://www.medworm.com/index.php?rid=5374735&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007125%2Fabstract%3Frss%3Dyes Highlights: ► ATP release by erythrocytes is attenuated in cells of Pannexin1 deficient mice. ► The Panx1−/− cells reveal a second Panx1 independent pathway for ATP release. ► The alternate pathway is activated by iloprost and inhibited by dipyridamole. ► The alternate release mechanism does not allow for the uptake of extracellular dyes. ► Glibenclamide inhibits Panx1 in the same concentration range as it inhibits CFTR channels.Abstract: Erythrocytes are exceptionally suited for analysis of non-exocytotic release mechanisms of ATP, because these cells under physiological conditions lack vesicles. Previous studies have indicated, that Pannexin1 (Panx1) provides a key ATP permeation pathway in many cell types, including human and frog erythrocytes. Here we show that erythrocyt... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374735 Mon, 03 Oct 2011 04:00:00 +0100 5374735 http://www.medworm.com/index.php?rid=5374733&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007095%2Fabstract%3Frss%3Dyes Highlights: ► Heparan sulfate (HS) biosynthesis is a complex multi-step process. ► N-Deacetylase–N-sulfotransferase (NDST) converts GlcNHAc to residues. ► NDST is considered as a gateway enzyme because it carries out the first modification. ► We show that O-sulfation does not inhibit NDST and NDST can also catalyze maturation. ► We redefine the dynamic role of NDST in the GAGOSOME.Abstract: Several biologically important growth factor–heparan sulfate (HS) interactions are regulated by HS sulfation patterns. However, the biogenesis of these combinatorial sulfation patterns is largely unknown. N-Deacetylase/N-sulfotrasferase (NDST) converts N-acetyl-d-glucosamine residues to N-sulfo-d-glucosamine residues. This enzyme is suggested to be a gateway enzyme because N-sulfation dict... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374733 Mon, 03 Oct 2011 04:00:00 +0100 5374733 http://www.medworm.com/index.php?rid=5374724&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007083%2Fabstract%3Frss%3Dyes In this study, we report that Nef suppressed LTR-driven transcription only in the presence of HIV-1 Tat, which was localized to the cytoplasm and degraded by the proteasome. However, the depletion of Hsp70 was found to reduce the suppressive effect of Nef on HIV-1 gene expression. These results suggest that Nef suppresses Hsp70-mediated HIV-1 Tat activation.Structured summary of protein interactions: Tat and Nefcolocalize by fluorescence microscopy(View interaction)Hsp70physically interacts with Tat by anti tag coimmunoprecipitation(View interaction) (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374724 Thu, 29 Sep 2011 04:00:00 +0100 5374724 http://www.medworm.com/index.php?rid=5374723&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100706X%2Fabstract%3Frss%3Dyes Highlights: ► CKII inhibition induced acetylation of p53 at K382 in HCT116 and HEK293 cells. ► This acetylation was suppressed by SIRT1 activation. ► CKII interacted with SIRT1 and CKII inhibition reduced SIRT1 activity. ► SIRT1 overexpression antagonized CKII inhibition-mediated cellular senescence. ► Thus, CKII inhibition stabilizes p53 by downregulating SIRT1 during senescence.Abstract: Cellular senescence is thought to be an important tumor suppression process in vivo. We have previously shown that p53 activation is necessary for CKII inhibition-mediated cellular senescence. Here, CKII inhibition induced acetylation of p53 at K382 in HCT116 and HEK293 cells. This acetylation event was suppressed by SIRT1 activation. CKIIα and CKIIβ were co-immunoprecipitated with SIRT1 in a... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5374723 Thu, 29 Sep 2011 04:00:00 +0100 5374723 http://www.medworm.com/index.php?rid=5310488&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007071%2Fabstract%3Frss%3Dyes Highlights: ► Fe65 directly interacts with the intracellular domains of LRP1 (LICD) and APP (AICD). ► Fe65/LICD interaction depends on tyrosine phosphorylation in the 2nd NPVY motif. ► Mutations of two Fe65 arginines impair complex formation with phosphorylated LICD. ► Fe65-PTB1 and Fe65-PTB2 are flexibly linked and can interact as independent modules.Abstract: Neuronal Fe65 is a central adapter for the intracellular protein network of Alzheimer’s disease related amyloid precursor protein (APP). It contains a unique tandem array of phosphotyrosine-binding (PTB) domains that recognize NPXY internalization motifs present in the intracellular domains of APP (AICD) and the low-density lipoprotein receptor-related protein LRP1 (LICD). The ternary APP/Fe65/LRP1 complex is an important ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310488 Thu, 29 Sep 2011 04:00:00 +0100 5310488 http://www.medworm.com/index.php?rid=5310506&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007058%2Fabstract%3Frss%3Dyes Highlights: ► Hepatitis B virus pregenomic RNA harbors interspersed splicing activator and repressor domains. ► Two intronic splicing activators in pregenomic RNA function independently of exonic splicing regulatory sequences. ► These activator sequences can stimulate splicing even when inside a heterologous intron.Abstract: HBV particles with genome derived from spliced mRNAs accumulate in patients with virus-derived severe liver necrosis and fibrosis. We investigated the role of an intronic element (intronic splicing silencer-long, ISSL) on splicing of HBV minigene transcripts. Removal of the entire ISSL showed two-fold increase in splicing while shorter deletions within ISSL indicated isolated clusters of activator and repressor domains. Activator domains stimulated splicing in pr... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310506 Wed, 28 Sep 2011 04:00:00 +0100 5310506 http://www.medworm.com/index.php?rid=5310505&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007046%2Fabstract%3Frss%3Dyes We examined the influence of iron levels on the abundance of Cir1. ► Iron deprivation results in reduced abundance of Cir1. ► Cir1 stability is also regulated by redox conditions and proteasome activity.Abstract: The GATA-type, zinc-finger protein Cir1 regulates iron uptake, iron homeostasis and virulence factor expression in the fungal pathogen Cryptococcus neoformans. The mechanisms by which Cir1 senses iron availability, although as yet undefined, are important for understanding the proliferation of the fungus in mammalian hosts. We investigated the influence of iron availability on Cir1 and found that the abundance of the protein decreases upon iron deprivation. This destabilization was influenced by reducing conditions and by inhibition of proteasome function. The combined data su... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310505 Wed, 28 Sep 2011 04:00:00 +0100 5310505 http://www.medworm.com/index.php?rid=5310503&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007022%2Fabstract%3Frss%3Dyes Highlights: ► We model the effect of Trx-1 on MMP-9 expression and involvement in breast cancer. ► Trx-1 stimulates MMP-9 expression by increasing NF-κB mediated transcription. ► Trx-1 de-regulates the MMP-9/TIMP-1 equilibrium and promotes MMP-9-dependent invasion. ► Trx-1 effects on MMP-9 are reversed by dominant negative Trx-1 and NF-κB inhibitors. ► Trx-1 and NF-κB are targets for reducing MMP-9 involvement in breast cancer.Abstract: Increased expression of thioredoxin (Trx)-1 and matrix metalloproteinase (MMP)-9 associates with malignant breast cancer progression. Here, we describe a functional relationship between Trx-1 and MMP-9 in promoting MDA-MB-231 breast cancer cell invasive behaviour. Trx-1 overexpression stimulated MMP-9 expression, de-regulated the MMP-9/TIMP-1 e... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310503 Tue, 27 Sep 2011 04:00:00 +0100 5310503 http://www.medworm.com/index.php?rid=5256982&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100679X%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5256982 Mon, 26 Sep 2011 23:43:02 +0100 5256982 http://www.medworm.com/index.php?rid=5310504&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007034%2Fabstract%3Frss%3Dyes Highlights: ► Progression of the VLCFA elongation cycle enhances ELOVL7 activity. ► ELOVL7 activity can be measured by reconstituting into proteoliposomes. ► Purified ELOVL7 exhibited high activity toward C18-CoA. ► Purified ELOVL7 exhibited Km values for its substrates in the μM order.Abstract: Very long-chain fatty acids (VLCFAs) have a variety of physiological functions and are related to numerous disorders. The key step of VLCFA elongation is catalyzed by members of the elongase family, ELOVLs. Mammals have seven ELOVLs (ELOVL1-7), yet none of them has been purified and analyzed. In the presented study we purified ELOVL7 and measured its activity by reconstituting it into proteoliposomes. Purified ELOVL7 exhibited high activity toward acyl-CoAs with C18 carbon chain length. Th... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310504 Fri, 23 Sep 2011 04:00:00 +0100 5310504 http://www.medworm.com/index.php?rid=5310476&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007010%2Fabstract%3Frss%3Dyes Cancer patients very often experience spread of tumor cells to secondary locations far-removed from the primary tumor center. In fact more than 90% of cancer deaths are caused by disseminating tumor cells . Research of the last years identified various steps of the metastatic cascade that includes cell invasion, survival in vascular and lymphatic space and colonization and tumor progression in distant organs. These steps are regulated by a class of metastasis effector genes both positively and negatively . Genes that inhibit metastasis but do not affect primary tumor development are called metastasis suppressor genes. This FOCUS ON…assembles a series of mini-reviews providing perspective on some of these genes, on the function of their products and therapeutic efficacy of their targeting... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310476 Thu, 22 Sep 2011 04:00:00 +0100 5310476 http://www.medworm.com/index.php?rid=5310502&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311007009%2Fabstract%3Frss%3Dyes Highlights: ► Non-natural sialic acids of the Kv3.1 glycoprotein modulate channel activation rates. ► Non-natural sialic acids of the Kv3.1 glycoprotein alter channel inactivation rates. ► The N-acyl side chain of sialic acids is connected to gating of the Kv3.1 channel.Abstract: The sialic acid of complex N-glycans can be biochemically engineered by substituting the physiological precursor N-acetylmannosamine with non-natural N-acylmannosamines. The Kv3.1 glycoprotein, a neuronal voltage-gated potassium channel, contains sialic acid. Western blots of the Kv3.1 glycoprotein isolated from transfected B35 neuroblastoma cells incubated with N-acylmannosamines verified sialylated N-glycans attached to the Kv3.1 glycoprotein. Outward ionic currents of Kv3.1 transfected B35 cells treated w... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310502 Wed, 21 Sep 2011 04:00:00 +0100 5310502 http://www.medworm.com/index.php?rid=5310501&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311006971%2Fabstract%3Frss%3Dyes Highlights: ► We have analyzed the Wurst requirement for airway liquid-clearance and air-filling in Drosophila. ► Wurst activity is required in tracheal cells at the final embryonic stage 17. ► Wurst and Dynamin are required for endocytosis-mediated airway liquid-clearance at stage 17. ► Apical Wurst localization in tracheal cells is involved in airway liquid-clearance. ► Wurst is a key regulator for tracheal physiology in Drosophila.Abstract: At the end of embryogenesis, Drosophila and mammalian airways convert from liquid-filled to air-filled tubes. This process is regulated by Clathrin-mediated endocytosis. However, these molecular mechanisms are poorly understood. In Drosophila, the DnaJ transmembrane protein Wurst interacts with Clathrin and Hsc70 to mediate early steps of e... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310501 Tue, 20 Sep 2011 04:00:00 +0100 5310501 http://www.medworm.com/index.php?rid=5310500&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931100696X%2Fabstract%3Frss%3Dyes In this study, we used small interfering RNA techniques to knockdown ARNT2 expression in MCF7 human breast cancer cells, and found that an almost 40% downregulation of ARNT2 mRNA expression increased the expression of sensitive to apoptosis gene (3.36-fold), and decreased the expression of von Hippel-Lindau (0.27-fold) and matrix metalloproteinase-1 (0.35-fold). The metabolite analysis revealed the contents of glucose, glycine, betaine, phosphocholine, pyruvate and lactate involved in the hypoxia-inducible factor (HIF)-1-dependent glycolytic pathway were significantly lower in cells treated with siARNT2. Our results suggested that ARNT2 might play an important role in the modulation of HIF-1-regulated signaling and metabolism. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310500 Tue, 20 Sep 2011 04:00:00 +0100 5310500 http://www.medworm.com/index.php?rid=5310499&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311006946%2Fabstract%3Frss%3Dyes Highlights: ► MiR-143 regulates adipogenic differentiation through regulating PTN expression. ► PTN is identified as a direct target of miR-143 and the target site of miR-143 is located in the coding region of PTN. ► The rare codons upstream of miR-143 target site are required for miR-143-mediated translational knockdown of PTN.Abstract: Adipogenic differentiation of preadipocytes is a complex process regulated by various factors including miRNAs and cytokines. MiR-143 is a well known miRNA that enhances adipogenesis. Pleiotrophin (PTN), a heparin-binding growth factor, plays a negative role in adipogenesis. In this investigation, we demonstrate that PTN is a target gene of miR-143 during adipogenic differentiation in 3T3-L1 preadipocytes. MiR-143 down regulates PTN expression throug... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310499 Tue, 20 Sep 2011 04:00:00 +0100 5310499 http://www.medworm.com/index.php?rid=5310487&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311006752%2Fabstract%3Frss%3Dyes Highlights: ► Glucocorticoid reduced the BDNF-increased synapse via inhibiting activation of ERK. ► BDNF-dependent interaction of Shp2 with TrkB was diminished by glucocorticoid. ► Glucocorticoid reduced BDNF-stimulated ERK via inhibiting the Shp2-TrkB interaction.Abstract: Increased glucocorticoids (GCs) have been implicated in the pathophysiology of depressive disorder. We previously found that dexamethasone (DEX, a synthetic GC) repressed brain-derived neurotrophic factor (BDNF)-induced synaptic proteins via suppressing extracellular signal-regulated protein kinase (ERK) signaling. Here, we investigated the possible involvement of Src homology-2 domain-containing phosphatase2 (Shp2), an ERK signaling mediator. We found that DEX suppressed Shp2 interaction with TrkB, a receptor for... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310487 Tue, 20 Sep 2011 04:00:00 +0100 5310487 http://www.medworm.com/index.php?rid=5310486&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311006958%2Fabstract%3Frss%3Dyes Highlights: ► The 140-kDa beta-isoform of neuronal nitric oxide synthase (nNOS) lacks the N-terminal PDZ-domain. ► Co-expression of beta- and 160-kDa alpha-isoforms in skeletal muscles of mice. ► Sarcolemmal co-localization of alpha- and beta-isoforms of nNOS. ► Association of the nNOS alpha- and beta-isoforms revealed by co-immunopreciptation.Abstract: In skeletal muscles, the expression of neuronal NO synthase (nNOS) isoforms is uncharacterized at the protein level. We therefore conducted epitope mapping with anti-peptide-antibodies. Antibodies specific for the nNOS N-terminus recognized the 160-kDa alpha-isoform. In contrast, antibodies against the middle portion or the C-terminus of nNOS bound additionally to the truncated 140-kDa beta-isoform which lacks the PDZ-domain present... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310486 Tue, 20 Sep 2011 04:00:00 +0100 5310486 http://www.medworm.com/index.php?rid=5310498&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311006922%2Fabstract%3Frss%3Dyes Highlights: ► The role of the metal-ion in the catalytic domain closure of IPMDH has been investigated. ► SAXS studies of the Thermus thermophilus enzyme showed no domain closure without the metal. ► Only the metal–IPM complex is efficient in stabilizing the native E. coli enzyme conformation. ► FRET studies with both IPMDHs confirm the importance of the metal. ► A possible atomic level explanation of the metal-effect is given.Abstract: X-ray structures of 3-isopropylmalate dehydrogenase (IPMDH) do not provide sufficient information on the role of the metal-ion in the metal–IPM assisted domain closure. Here solution studies were carried out to test its importance. Small-angle X-ray scattering (SAXS) experiments with the Thermus thermophilus enzyme (complexes with single subst... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310498 Mon, 19 Sep 2011 04:00:00 +0100 5310498 http://www.medworm.com/index.php?rid=5310497&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579311006910%2Fabstract%3Frss%3Dyes Highlights: ► Linalool is an aromatic monoterpene abundant in teas and essential oils. ► Linalool feeding significantly lowered LDL cholesterol concentrations in mice. ► Linalool reduced the expression of HMG-CoA reductase by SREBP-2-dependent mechanism. ► Linalool also induced ubiquitin-dependent proteolysis of the HMG-CoA reductase. ► These suggest food compounds with a pleasant scent exert beneficial metabolic effects.Abstract: We investigated hypocholesterolemic mechanisms of linalool, an aromatic anti-oxidative monoterpene, which is abundant in teas and essential oils. Oral administration of linalool to mice for 6weeks significantly lowered total and low-density lipoprotein cholesterol concentrations, and HMG-CoA reductase protein expression (−46%; P (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=5310497 Mon, 19 Sep 2011 04:00:00 +0100 5310497