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. Thu, 18 Mar 2010 16:19:45 +0100 http://www.medworm.com/index.php?rid=3373588&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001869%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373588 Wed, 17 Mar 2010 16:26:11 +0100 3373588 http://www.medworm.com/index.php?rid=3369596&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001778%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369596 Tue, 16 Mar 2010 17:38:59 +0100 3369596 http://www.medworm.com/index.php?rid=3373604&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931000164X%2Fabstract%3Frss%3Dyes Abstract: Cellular homeostasis is linked tightly to mitochondrial functions. Some damage to mitochondrial proteins and nucleic acids can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy. Mitochondrial dysfunction is one of the key aspects of the pathobiology of neurodegenerative disease. Parkin, an E3 ligase located in the cytosol and originally discovered as mutated in monogenic forms of Parkinson’s disease (PD), was found recently to translocate specifically to uncoupled mitochondria and to induce their autophagy. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373604 Thu, 25 Feb 2010 00:00:00 +0100 3373604 http://www.medworm.com/index.php?rid=3373592&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001651%2Fabstract%3Frss%3Dyes Abstract: Autophagosomes (APs) are unique organelles that enwrap cytoplasmic components when necessary. APs then fuse with lysosomes and enclosed materials are degraded. Although approximately 30 autophagy-related genes (ATG) required for AP formation have been identified, fundamental questions on the membrane source or dynamics during the formation remain unresolved. Here, we present a comprehensive overview of the putative membrane sources identified to date. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373592 Thu, 25 Feb 2010 00:00:00 +0100 3373592 http://www.medworm.com/index.php?rid=3373594&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001584%2Fabstract%3Frss%3Dyes Abstract: Autophagy initiation is strictly dependent on phosphatidylinositol 3-phosphate (PI3P) synthesis. PI3P production is under tight control of PI3Kinase, hVps34, in complex with Beclin-1. Mammalian cells express several PI3P phosphatases that belong to the myotubularin family. Even though some of them have been linked to serious human diseases, their cellular function is largely unknown. Two recent studies indicate that PI3P metabolism involved in autophagy initiation is further regulated by the PI3P phosphatases Jumpy and MTMR3. Additional pools of PI3P, upstream of mTOR and on the endocytic pathway, may modulate autophagy indirectly, suggesting that other PI3P phosphatases might be involved in this process. This review sums up our knowledge on PI3P phosphatases and discusses the re... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373594 Wed, 24 Feb 2010 00:00:00 +0100 3373594 http://www.medworm.com/index.php?rid=3369630&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001602%2Fabstract%3Frss%3Dyes Abstract: Vitellogenins and other large lipid transfer proteins (LLTP) are well known to play significant roles in the development, metabolism and reproduction of animals. Comparative genomics and phylogenetic analyses of LLTPs using the most comprehensive dataset in metazoans to date are carried out. Our analyses demonstrate that LLTP genes arose significantly earlier, and are more widespread than previously proposed – being present in numerous additional bilaterian and non-bilaterian lineages. A hypothesis is advanced that the most ancestral animal LLTP gene is Vtg, while loss of domains occurred at the bilaterians stem giving rise to apolipoprotein and microsomal triglyceride transfer proteins genes. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369630 Wed, 24 Feb 2010 00:00:00 +0100 3369630 http://www.medworm.com/index.php?rid=3369604&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001596%2Fabstract%3Frss%3Dyes Abstract: S100 proteins are a subfamily of the EF-hand type calcium sensing proteins, the exact biological functions of which have not been clarified yet. In this work, we have identified Cyclophilin 40 (CyP40) and FKBP52 (called immunophilins) as novel targets of S100 proteins. These immunophilins contain a tetratricopeptide repeat (TPR) domain for Hsp90 binding. Using glutathione-S transferase pull-down assays and immunoprecipitation, we have demonstrated that S100A1 and S100A2 specifically interact with the TPR domains of FKBP52 and CyP40 in a Ca2+-dependent manner, and lead to inhibition of the CyP40–Hsp90 and FKBP52–Hsp90 interactions. These findings have suggested that the Ca2+/S100 proteins are TPR-targeting regulators of the immunophilins–Hsp90 complex formations.Structured s... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369604 Wed, 24 Feb 2010 00:00:00 +0100 3369604 http://www.medworm.com/index.php?rid=3369603&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001626%2Fabstract%3Frss%3Dyes Abstract: The extended Fes-CIP4 homology (EFC)/FCH-BAR (F-BAR) domain tubulates membranes. Overexpression of the pacsin2 EFC/F-BAR domain resulted in tubular localization inside cells and deformed liposomes into tubules in vitro. We found that overexpression of the pacsin2 EFC/F-BAR domain induced cellular microspikes, with the pacsin2 EFC/F-BAR domain concentrated at the neck. The hydrophobic loops and the basic amino-acid residues on the concave surface of the pacsin2 EFC/F-BAR domain are essential for both the microspike formation and tubulation. Since the curvature of the neck of the microspike and that of the tubulation share similar geometry, the pacsin2 EFC/F-BAR domain is considered to facilitate both microspike formation and tubulation.Structured summary: MINT-7710892: EFCS pacsin... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369603 Wed, 24 Feb 2010 00:00:00 +0100 3369603 http://www.medworm.com/index.php?rid=3369602&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001614%2Fabstract%3Frss%3Dyes Abstract: Class IIa histone deacetylases (HDACs) -4, -5, -7 and -9 undergo signal-dependent nuclear export upon phosphorylation of conserved serine residues that are targets for 14-3-3 binding. Little is known of other mechanisms for regulating the subcellular distribution of class IIa HDACs. Using a biochemical purification strategy, we identified protein kinase C-related kinase-2 (PRK2) as an HDAC5-interacting protein. PRK2 and the related kinase, PRK1, phosphorylate HDAC5 at a threonine residue (Thr-292) positioned within the nuclear localization signal (NLS) of the protein. HDAC7 and HDAC9 contain analogous sites that are phosphorylated by PRK, while HDAC4 harbors a non-phosphorylatable alanine residue at this position. We provide evidence to suggest that the unique phospho-acceptor co... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369602 Wed, 24 Feb 2010 00:00:00 +0100 3369602 http://www.medworm.com/index.php?rid=3373589&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001572%2Fabstract%3Frss%3Dyes Since the discovery of yeast autophagy-related genes (current ATG genes) in the early 1990s, the autophagy research field has grown exponentially. The number of published papers related to autophagy was less than 100 per year before 2000; however, in 2009, it exceeded 1600. Moreover, autophagy has also been discussed not only in scientific journals. There is a very popular Japanese comic (manga) magazine, “Weekly Shonen (means boys) Jump”, with a weekly a circulation of more than 2 million. In two issues in 2009, autophagy appeared in a story in which a hero fought against an enemy. The hero was starved, but was activated by inducing autophagy (unfortunately, the effect did not last long). This magazine told more than 2 million children (and some adults) that we have a unique strategy,... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373589 Tue, 23 Feb 2010 00:00:00 +0100 3373589 http://www.medworm.com/index.php?rid=3293899&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001237%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293899 Mon, 22 Feb 2010 16:37:23 +0100 3293899 http://www.medworm.com/index.php?rid=3369629&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001559%2Fabstract%3Frss%3Dyes Abstract: MotA and MotB form the proton-channel complex of the proton-driven bacterial flagellar motor. A plug segment of Escherichia coli MotB suppresses proton leakage through the MotA/B complex when it is not assembled into the motor. Using a ratiometric pH indicator protein, pHluorin, we show that the proton-conductivity of a Salmonella MotA/B complex not incorporated into the motor is two orders of magnitude lower than that of a complex that is incorporated and activated. This leakage is, however, significant enough to change the cytoplasmic pH to a level at which the chemotaxis signal transduction system responds. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369629 Mon, 22 Feb 2010 00:00:00 +0100 3369629 http://www.medworm.com/index.php?rid=3369628&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001456%2Fabstract%3Frss%3Dyes Abstract: Viperin, an interferon-inducible antiviral protein, is shown to bind an iron-sulfur cluster, based on iron analysis as well as UV–Vis and electron paramagnetic resonance spectroscopic data. The reduced protein contains a [4Fe-4S]1+ cluster whose g-values are altered upon addition of S-adenosylmethionine (SAM), consistent with SAM coordination to the cluster. Incubation of reduced viperin with SAM results in reductive cleavage of SAM to produce 5′-deoxyadenosine (5′-dAdo), a reaction characteristic of the radical SAM superfamily. The 5′-dAdo cleavage product was identified by a combination of HPLC and mass spectrometry analysis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369628 Mon, 22 Feb 2010 00:00:00 +0100 3369628 http://www.medworm.com/index.php?rid=3369627&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001468%2Fabstract%3Frss%3Dyes Abstract: Mitochondrial peroxiredoxin 3 (Prx 3) is rapidly oxidized in cells exposed to phenethyl isothiocyanate (PEITC) and auranofin (AFN), but the mechanism of oxidation is unclear. Using HL-60 cells deplete of mitochondrial DNA we show that peroxiredoxin 3 oxidation and cytotoxicity requires a functional respiratory chain. Thioredoxin reductase (TrxR) could be inhibited by up to 90% by auranofin without direct oxidation of peroxiredoxin 3. However, inhibition of thioredoxin reductase promoted peroxiredoxin 3 oxidation and cytotoxicity in combination with phenethyl isothiocyanate or antimycin A. We conclude that rapid peroxiredoxin 3 oxidation occurs as a consequence of increased oxidant production from the mitochondrial respiratory chain. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369627 Mon, 22 Feb 2010 00:00:00 +0100 3369627 http://www.medworm.com/index.php?rid=3369626&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001444%2Fabstract%3Frss%3Dyes Abstract: Initial characterizations of live-Salmonella-containing early (LSEP) and late phagosomes (LSLP) in macrophages show that both phagosomes retain Rab5 and EEA1. In addition, LSEP specifically contain transferrin receptor whereas LSLP possess relatively more rabaptin-5. In contrast to LSLP, late-Salmonella-containing vacuoles in epithelial cells show significantly reduced levels of Rab5 and EEA1. Subsequent results demonstrate that both phagosomes efficiently fuse with early endosomes (EE). In contrast to LSEP, fusion between LSLP and EE is insensitive to ATPγS treatment. Furthermore, LSLP fuses with EE in absence of NEM-sensitive fusion factor (NSF) as well as in the presence of NSF:D1EQ mutant demonstrating that LSLP fusion with EE is NSF independent. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369626 Mon, 22 Feb 2010 00:00:00 +0100 3369626 http://www.medworm.com/index.php?rid=3369625&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001432%2Fabstract%3Frss%3Dyes Abstract: Here we report that deletion of SOD1, the Cu,Zn-superoxide dismutase in Saccharomyces cerevisiae is sensitive to cell wall-perturbing agents, such as Calcofluor white and Congo red. The sensitivity was restored by retransformation with wild type SOD1 or the addition of N-acetylcysteine or reduced glutathione to the medium. Additionally, the accumulation of reactive oxygen species was observed in sod1Δ mutant in the presence of Calcofluor white or Congo red. Cell wall analysis indicated an increase of cell wall chitin and cell wall thickness in sod1Δ mutant compared to wild type. These results indicate a novel direct connection between antioxidative functions and cell wall homeostasis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369625 Mon, 22 Feb 2010 00:00:00 +0100 3369625 http://www.medworm.com/index.php?rid=3369624&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001420%2Fabstract%3Frss%3Dyes Abstract: Malonyl-CoA-acyl carrier protein transacylase (MCAT) transfers the malonyl group from malonyl-CoA to holo-acyl carrier protein (ACP), and since malonyl-ACP is a key building block for fatty-acid biosynthesis it is considered as a promising antibacterial target. The crystal structures of MCAT from Staphylococcus aureus and Streptococcus pneumoniae have been determined at 1.46 and 2.1Å resolution, respectively. In the SaMCAT structure, the N-terminal expression peptide of a neighboring molecule running in the opposite direction of malonyl-CoA makes extensive interactions with the highly conserved “Gly-Gln-Gly-Ser-Gln” stretch, suggesting a new design platform. Mutagenesis results suggest that Ser91 and His199 are the catalytic dyad. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369624 Mon, 22 Feb 2010 00:00:00 +0100 3369624 http://www.medworm.com/index.php?rid=3369617&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931000147X%2Fabstract%3Frss%3Dyes Abstract: The CDC25B phosphatase regulates the activation of CDK1–Cyclin B at the onset of mitosis, being a key target of the checkpoint pathways activated by cellular stress and DNA damage. Previous work has reported that checkpoint activation induces the sequestration of CDC25B in the cytoplasm. Here we show that in response to UV irradiation, the levels of CDC25B protein can be downregulated independently of classical checkpoints pathways such as p53, ATM/ATR and p38 MAPK. We also show that translational repression mediated by eIF2α phosphorylation regulates CDC25B expression levels. Taken together, our results illustrate a new mechanism of CDC25B regulation in response to stress. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369617 Mon, 22 Feb 2010 00:00:00 +0100 3369617 http://www.medworm.com/index.php?rid=3369601&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001560%2Fabstract%3Frss%3Dyes Abstract: HlyU is a transcription factor of the ArsR/SmtB family and activates the expression of the pathogenic Vibrio vulnificus RTX toxin. In contrast to the other metal-responding ArsR/SmtB proteins, HlyU does not sense metal ions. To provide its structural information, we elucidated the crystal structure of HlyU from V. vulnificus CMCP6 (HlyU_Vv). The monomeric HlyU_Vv architecture of five α-helices and two β-strands, some of which constitute a typical DNA-binding winged helix-turn-helix (wHTH) motif, is very similar to that of other transcription regulators. Nonetheless, the homo-dimeric HlyU_Vv structure shows several different, three-dimensional features in the spatial position and the detailed dimeric interaction, which were not observed in the modeling study based on the same pr... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369601 Mon, 22 Feb 2010 00:00:00 +0100 3369601 http://www.medworm.com/index.php?rid=3369600&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001481%2Fabstract%3Frss%3Dyes Abstract: Heparin Binding Hemagglutinin A (HBHA) is hitherto the sole virulence factor associated with tuberculosis dissemination from the lungs, the site of primary infection, to epithelial cells. We have previously reported the solution structure of HBHA, a dimeric and elongated molecule. Since oligomerisation of HBHA is associated with its ability to induce bacterial agglutination, we investigated this process using experimental and modelling techniques. We here identified a short segment of HBHA whose presence is mandatory for the stability of folded conformation, whose denaturation is a reversible two-state process. Our data suggest that agglutination-driven cell–cell interactions do not occur via association of HBHA monomers, nor via association of HBHA dimers and open the scenario... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369600 Mon, 22 Feb 2010 00:00:00 +0100 3369600 http://www.medworm.com/index.php?rid=3369623&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001390%2Fabstract%3Frss%3Dyes Abstract: The giant protein titin, which comprises immunoglobulin (Ig) domains, acts as a bidirectional spring in muscle. The unfolding of Ig domains has been extensively studied, but their dynamics under native states have not been well-characterized. We performed molecular dynamics simulation on a single titin Ig domain and multi-domains. Mobile regions displaying concerted motions were identified. The dynamics of Ig domains are constrained by evolutionary pressures, in such a way that global dominant motion is conserved, yet different flexibilities within Ig domains and in linkers connecting neighbouring domains were observed. We explain these heterogeneous conserved dynamics in relation to sequence conservation across species and the sequence diversity among neighbouring Ig domains. (S... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369623 Thu, 18 Feb 2010 00:00:00 +0100 3369623 http://www.medworm.com/index.php?rid=3369622&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001419%2Fabstract%3Frss%3Dyes Abstract: Like many other aerobic archaea, the hyperthermophile Sulfolobus solfataricus possesses a gene cluster encoding components of a putative 2-oxoacid dehydrogenase complex. In the current paper, we have cloned and expressed the first two genes of this cluster and demonstrate that the protein products form an α2β2 hetero-tetramer possessing the catalytic activity characteristic of the first component enzyme of an acetoin dehydrogenase multienzyme complex. This represents the first report of an acetoin multienzyme complex in archaea, and contrasts with the branched-chain 2-oxoacid dehydrogenase complex activities characterised in two other archaea, Thermoplasma acidophilum and Haloferax volcanii. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369622 Thu, 18 Feb 2010 00:00:00 +0100 3369622 http://www.medworm.com/index.php?rid=3369621&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001407%2Fabstract%3Frss%3Dyes Abstract: The pleckstrin homology (PH) domain-containing protein casein kinase 2 interacting protein-1 (CKIP-1) plays an important role in regulation of bone formation and muscle differentiation. How CKIP-1 localization is determined remains largely unclear. We observed that isolated CKIP-1-PH domain was predominantly localized in the nucleus and the C-terminus of CKIP-1 counteracted its nuclear localization. The net charge of basic residues and a serine-rich motif within the PH domain plays a pivotal role in the localization switch of both full-length CKIP-1 and the isolated PH domain. We propose that the N-terminal PH domain and C-terminal auto-inhibitory region of CKIP-1 coordinate to determine its subcellular localization and the nucleus–plasma membrane shuttling. (Source: FEBS Lette... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369621 Thu, 18 Feb 2010 00:00:00 +0100 3369621 http://www.medworm.com/index.php?rid=3369620&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001389%2Fabstract%3Frss%3Dyes Abstract: A link between cellular uptake of high density lipoprotein (HDL) and regulation of sterol regulatory element-binding protein-1 (SREBP-1) was investigated in vitro. HDL decreased nuclear SREBP-1 levels as well as SREBP-1 target gene expression in HepG2 and HEK293 cells. However, HDL did not repress an exogenously expressed, constitutively active form of SREBP-1. HDL increased cellular cholesterol levels, and cellular cholesterol depletion by methyl-β-cyclodextrin abolished the effects of HDL. These results suggest that HDL inhibits the activation of SREBP-1 through a cholesterol-dependent mechanism, which may play an important role in regulating lipid synthetic pathways mediated by SREBP-1. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369620 Thu, 18 Feb 2010 00:00:00 +0100 3369620 http://www.medworm.com/index.php?rid=3369619&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001377%2Fabstract%3Frss%3Dyes Abstract: Pheromone biosynthesis-activating neuropeptide (PBAN) and pyrokinins belong to a family of insect peptide hormones that have a common FXPRLamide C-terminal ending. The G-protein-coupled receptors (GPCRs) for this peptide family were first identified from a moth and Drosophila with sequence similarity to neuromedin U receptors from vertebrates. We have characterized the PBAN-receptor (PBAN-R or PR) active binding domains using chimeric GPCRs and proposed that extracellular loop 3 is critical for ligand selection. Here, we characterized the 3rd extracellular domain of PBAN-R through site-directed point mutations. Results are discussed in context of the structural features required for receptor activation using receptor activation experiments and in silico computational modeling. Th... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369619 Mon, 15 Feb 2010 00:00:00 +0100 3369619 http://www.medworm.com/index.php?rid=3369618&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001316%2Fabstract%3Frss%3Dyes Abstract: The crystal structures of a carbohydrate-binding module (CBM) family 28 domain of endoglucanase Cel5A from Clostridium josui have been determined in ligand-free and complex forms with cellobiose, cellotetraose, and cellopentaose as the first complex structures of this family. In the cleft of a β-sandwich fold, the ligands are recognized by stacking interactions and hydrogen bonds. Conformations of the bound cellooligosaccharides are similar to those in crystals and solution but clearly different from the cellulose structure. Interestingly, the glucan chain bound on CBM28 is in the opposite direction of that bound to CBM17, although these families share significant structural similarity. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369618 Mon, 15 Feb 2010 00:00:00 +0100 3369618 http://www.medworm.com/index.php?rid=3369616&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931000133X%2Fabstract%3Frss%3Dyes Abstract: γ-Aminobutyric acid type A (GABAA) receptor β1 (gabrb1), a subunit of GABAA receptors involved in inhibitory effects on neurotransmission, was found to associate with the formation of protease-resistant prion protein in prion-infected neuroblastoma cells. Silencing of gabrb1 gene expression significantly decreased the abnormal prion protein level but paradoxically increased the normal prion protein level. Treatment with a gabrb1-specific inhibitor, salicylidene salicylhydrazide, dose-dependently decreased the abnormal prion protein level, but silencing of other GABAA receptor subunits’ gene expression and treatments with the receptor antagonists and agonists did not. Therefore, gabrb1 involvement in abnormal prion protein formation is independent of GABAA receptors. (Source: ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369616 Mon, 15 Feb 2010 00:00:00 +0100 3369616 http://www.medworm.com/index.php?rid=3369599&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001353%2Fabstract%3Frss%3Dyes Abstract: The putative CCDC106 protein was previously identified as a p53-interacting partner by automated yeast two-hybrid screening, but its sequence and function have not been validated experimentally. Here, we identified three variant transcripts of the CCDC106 gene; these transcripts differ in their second exons due to the use of different splice acceptor site, but encode an identical protein of 280 residues. A bipartite nuclear localisation signal at residues 151–164 mediates the nuclear localisation of CCDC106. Double immunofluorescence staining revealed the colocalisation of endogenous CCDC106 and p53 protein in nuclei. The in vivo interaction between CCDC106 and p53 was confirmed by a co-immunoprecipitation assay. Furthermore, we demonstrated that CCDC106 promotes the degradatio... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369599 Mon, 15 Feb 2010 00:00:00 +0100 3369599 http://www.medworm.com/index.php?rid=3373602&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001110%2Fabstract%3Frss%3Dyes Abstract: Autophagy is a highly conserved bulk protein degradation pathway responsible for the turnover of long-lived proteins, disposal of damaged organelles, and clearance of aggregate-prone proteins. Thus, inactivation of autophagy results in cytoplasmic protein inclusions, which are composed of misfolded proteins and excess accumulation of deformed organelles, leading to liver injury, diabetes, myopathy, and neurodegeneration. Although autophagy has been considered non-selective, growing lines of evidence indicate the selectivity of autophagy in sorting vacuolar enzymes and in the removal of aggregate-prone proteins, unwanted organelles and microbes. Such selectivity by autophagy enables diverse cellular regulations, similar to the ubiquitin–proteasome pathway. In this review, we int... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373602 Thu, 11 Feb 2010 00:00:00 +0100 3373602 http://www.medworm.com/index.php?rid=3369615&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001195%2Fabstract%3Frss%3Dyes Abstract: Here, we report Prostaglandin A2 (PGA2) induced binding of HSP70 to a novel site on φ1 SMAR1 5′ UTR which stabilizes the wild type transcript and leads to subsequent increase in SMAR1 protein levels. SMAR1 mediated cell cycle arrest is perturbed in PGA2-treated cells when HSP70 is knocked-down. Contrarily HSP70, unlike SMAR1, is overexpressed in breast cancers. We demonstrate that this is because of the inability of HSP70 to bind to the φ17 SMAR1 UTR variant which is the predominant form in breast cancers. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369615 Thu, 11 Feb 2010 00:00:00 +0100 3369615 http://www.medworm.com/index.php?rid=3369614&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001171%2Fabstract%3Frss%3Dyes Abstract: We have previously demonstrated that RNA interference-mediated suppression of xanthine dehydrogenase (XDH), the rate-limiting enzyme in purine degradation, causes defects in the normal growth and development of Arabidopsis thaliana. Here, we investigated a possible role for XDH in drought tolerance, since this enzyme is also implicated in plant stress responses and acclimatization. When XDH-suppressed lines were subjected to drought stress, plant growth was markedly reduced in conjunction with significantly enhanced cell death and H2O2 accumulation. This drought-hypersensitive phenotype was reversed by pretreatment with exogenous uric acid, the catalytic product of XDH. These results suggest that fully functional purine metabolism plays a role in the Arabidopsis drought acclimati... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369614 Thu, 11 Feb 2010 00:00:00 +0100 3369614 http://www.medworm.com/index.php?rid=3369613&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001183%2Fabstract%3Frss%3Dyes Abstract: The steroid receptor RNA activator gene (SRA1) encodes for a functional RNA (SRA) as well as a protein (SRAP). While several groups reported on SRA-RNA mechanism of action, SRAP exact function remains to be elucidated, mainly due to a lack of studies investigating the function of the protein independently of its RNA counterpart. Using two independent models to examine its specific functions, SRAP was found to enhance estrogen receptor alpha activity in a ligand and response-element dependent manner. Our data therefore suggest that both transcript and protein products of the SRA1 gene co-modulate the transcriptional activity of steroid receptors. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369613 Thu, 11 Feb 2010 00:00:00 +0100 3369613 http://www.medworm.com/index.php?rid=3369612&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001146%2Fabstract%3Frss%3Dyes Abstract: Insulin is a secreted peptide that controls glucose homeostasis in mammals, and insulin biosynthesis is regulated by glucose at many levels. Rodent insulin is encoded by two non-allelic genes. We have identified a novel splice variant of the insulin2 gene in mice that constitutes about 75% of total insulin2 mRNA. The alternate splicing does not alter the ORF but reduces the 5′UTR by 12 bases. A reporter gene containing the novel short 5′UTR, is more efficiently expressed in cells, suggesting that alternative splicing of insulin mRNA in mice could result in an additional level of regulation in insulin biosynthesis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369612 Thu, 11 Feb 2010 00:00:00 +0100 3369612 http://www.medworm.com/index.php?rid=3369611&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001158%2Fabstract%3Frss%3Dyes Abstract: A number of methods exist that use different approaches to assess geometric properties like the surface complementarity and atom packing at the protein–protein interface. We have developed two new and conceptually different measures using the Delaunay tessellation and interface slice selection to compute the surface complementarity and atom packing at the protein–protein interface in a straightforward manner. Our measures show a strong correlation among themselves and with other existing measures, and can be calculated in a highly time-efficient manner. The measures are discriminative for evaluating biological, as well as non-biological protein–protein contacts, especially from large protein complexes and large-scale structural studies (http://pallab.serc.iisc.ernet.in/nip_... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369611 Thu, 11 Feb 2010 00:00:00 +0100 3369611 http://www.medworm.com/index.php?rid=3369610&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001122%2Fabstract%3Frss%3Dyes Abstract: Proteins with Pumilio RNA binding domains (Puf proteins) are ubiquitous in eukaryotes. Some Puf proteins bind to the 3′-untranslated regions of mRNAs, acting to repress translation and promote degradation; others are involved in ribosomal RNA maturation. The genome of Trypanosoma brucei encodes eleven Puf proteins whose function cannot be predicted by sequence analysis. We show here that epitope-tagged TbPUF7 is located in the nucleolus, and associated with a nuclear cyclophilin-like protein, TbNCP1. RNAi targeting PUF7 reduced trypanosome growth and inhibited two steps in ribosomal RNA processing. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369610 Thu, 11 Feb 2010 00:00:00 +0100 3369610 http://www.medworm.com/index.php?rid=3369606&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001092%2Fabstract%3Frss%3Dyes Abstract: The molecular nature of the structure responsible for proton sensitivity in KcsA has been identified as a charge cluster that surrounds the inner helical bundle gate. Here, we show that this proton sensor can be modified to engineer a constitutively open form of KcsA, amenable to functional, spectroscopic and structural analyses. By combining charge neutralizations for all acidic and basic residues in the cluster at positions 25, 117–122 and 124 (but not E118), a mutant KcsA is generated that displays constitutively open channel activity up to pH 9. The structure of this mutant revealed that full opening appears to be inhibited by lattice forces since the activation gate seems to be only on the early stages of opening. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369606 Thu, 11 Feb 2010 00:00:00 +0100 3369606 http://www.medworm.com/index.php?rid=3369598&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001134%2Fabstract%3Frss%3Dyes In this study, we developed a novel binding assay, using purified proteins, for tracking the interaction between p53 and mortalin. Our results reveal that: (i) P53 binds to the peptide-binding site of mortalin which enhances the ability of the former to bind DNA. (ii) An additional previously unknown binding site for mortalin exists within the C-terminal domain of p53.Structured summary: MINT-7557591: p53 (uniprotkb:P04637) binds (MI:0407) to DnaK (uniprotkb:P0A6Y8) by affinity chromatography technology (MI:0004)MINT-7557644: mortalin (uniprotkb:P38646) binds (MI:0407) to p53 (uniprotkb:P04637) by pull down (MI:0096)MINT-7557580, MINT-7557611: p53 (uniprotkb:P04637) binds (MI:0407) to mortalin (uniprotkb:P38646) by affinity chromatography technology (MI:0004) (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369598 Thu, 11 Feb 2010 00:00:00 +0100 3369598 http://www.medworm.com/index.php?rid=3369597&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001109%2Fabstract%3Frss%3Dyes Abstract: Mutations in PTEN-induced putative kinase 1 (PINK1) cause recessive form of Parkinson’s disease (PD). PINK1 acts upstream of parkin, regulating mitochondrial integrity and functions. Here, we show that PINK1 in combination with parkin results in the perinuclear mitochondrial aggregation followed by their elimination. This elimination is reduced in cells expressing PINK1 mutants with wild-type parkin. Although wild-type PINK1 localizes in aggregated mitochondria, PINK1 mutants localization remains diffuse and mitochondrial elimination is not observed. This phenomenon is not observed in autophagy-deficient cells. These results suggest that mitophagy controlled by the PINK1/parkin pathway might be associated with PD pathogenesis.Structured summary: MINT-7557195: PINK1 (uniprotkb:Q... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369597 Thu, 11 Feb 2010 00:00:00 +0100 3369597 http://www.medworm.com/index.php?rid=3293939&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001080%2Fabstract%3Frss%3Dyes An unfortunate error occurred in the first sentence of the second paragraphin the Introduction. The sentence “The phosphagen kinase family includes the well-studied creatine kinase (CK) found only in vertebrates and arginine kinase (AK), which is most widely distributed in invertebrates, being present in deuterostomes, protostomes, basal metazoans, and some protozoans [3]”should read “The phosphagen kinase family includes the well-studied creatine kinase (CK), the sole PK in vertebrates and arginine kinase (AK), which is most widely distributed in invertebrates, being present in deuterostomes, protostomes, basal metazoans, and some protozoans [3].” (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293939 Wed, 10 Feb 2010 00:00:00 +0100 3293939 http://www.medworm.com/index.php?rid=3373600&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001079%2Fabstract%3Frss%3Dyes Abstract: Autophagy is a highly conserved, ubiquitous process that is responsible for the degradation of cytosolic components in response to starvation. Autophagy is generally considered to be non-selective; however, there are selective types of autophagy that use receptor and adaptor proteins to specifically isolate a cargo. One type of selective autophagy in yeast is the cytoplasm to vacuole targeting (Cvt) pathway. The Cvt pathway is responsible for the delivery of the hydrolase aminopeptidase I to the vacuole; as such, it is the only known biosynthetic pathway that utilizes the core machinery of autophagy. Nonetheless, it serves as a model for the study of selective autophagy in other organisms. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373600 Mon, 08 Feb 2010 00:00:00 +0100 3373600 http://www.medworm.com/index.php?rid=3293938&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001067%2Fabstract%3Frss%3Dyes Abstract: Inositol requiring enzyme-1α (IRE1α) is an ER-located transmembrane RNase whose activation leads to the production of the transcription factor X-box binding protein 1 (XBP1). Recently, we showed that the IRE1α–XBP1 pathway plays an essential role in the placenta. However, details of its function remain unclear. To address this point, we searched for IRE1α- or XBP1-regulated genes in the placenta, and identified the CEA family as a novel target of the IRE1α–XBP1 pathway. Moreover, PSG genes, which also belong to the CEA family, were up-regulated by XBP1. We have therefore identified a new aspect of the physiological function of the IRE1α–XBP1 pathway in the placenta. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293938 Mon, 08 Feb 2010 00:00:00 +0100 3293938 http://www.medworm.com/index.php?rid=3293900&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001055%2Fabstract%3Frss%3Dyes Each year we look forward and plan new strategies for the journal. We also take the time to look at the changes that we have made over the last years and evaluate their impact on FEBS Letters. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293900 Mon, 08 Feb 2010 00:00:00 +0100 3293900 http://www.medworm.com/index.php?rid=3373597&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000955%2Fabstract%3Frss%3Dyes Abstract: Autophagy is an evolutionarily conserved intracellular catabolic system. During Caenorhabditis elegans development, autophagy plays an important role in many physiological processes, including survival under starvation conditions, modulation of life span, and regulation of necrotic cell death caused by toxic ion-channel variants. Recently, it has been demonstrated that during embryogenesis, basal levels of autophagy selectively remove a group of proteins in somatic cells, including the aggregate-prone components of germline P granules. Degradation of these protein aggregates provides a genetic model to identify essential autophagy components and also to elucidate how the autophagic machinery selectively recognizes and degrades specific targets during animal development. (Source: ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373597 Fri, 05 Feb 2010 00:00:00 +0100 3373597 http://www.medworm.com/index.php?rid=3373590&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000931%2Fabstract%3Frss%3Dyes Abstract: Autophagy is a system for degradation of bulk cellular components in lytic compartments, vacuoles, or lysosomes when eukaryotic cells face with nutrient starvation. In this review, we focus on the pre-autophagosomal structure (PAS), a functional entity responsible for autophagosome formation in Saccharomyces cerevisiae, and discuss its relevance to autophagy in mammalian cells. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373590 Fri, 05 Feb 2010 00:00:00 +0100 3373590 http://www.medworm.com/index.php?rid=3369609&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931000102X%2Fabstract%3Frss%3Dyes Abstract: The yeast Saccharomyces cerevisiae is able to form complex multicellular structures called mats on low-density agar Petri plates. Mat formation strictly depends on Flo11p, a cell surface mannoprotein that mediates the adhesion of yeast cells to the agar surface. Here, we show that Swa2p, an auxilin ortholog required for clathrin-coated vesicle uncoating, is strictly required for biofilm formation. We show that the maturation and cellular levels of Flo11p are affected in Δswa2 cells, yet without compromising invasive growth. Both the TPR and J-domains of Swa2p, but not its clathrin-binding and ubiquitin-association motifs, are required for its function in Flo11p processing. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369609 Fri, 05 Feb 2010 00:00:00 +0100 3369609 http://www.medworm.com/index.php?rid=3369608&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001006%2Fabstract%3Frss%3Dyes Abstract: Oxysterols activating liver X receptors (LXRs) repress expression of pro-inflammatory genes and have anti-inflammatory effects. Here, we show for the first time that bone marrow-derived murine mast cells (BMMCs) predominantly express LXRβ. 25-hydroxycholesterol, a representative LXR activating oxysterol, suppressed IL-6 production and degranulation response in BMMCs following engagement of high-affinity IgE receptor (FcεRI). Interestingly, 25-hydroxycholesterol reduced cell-surface FcεRI expression by inhibiting assembly of FcεRIα and FcεRIβ. We demonstrate that LXR activation was involved in the suppression of IL-6 production in BMMCs, but that reduced FcεRI expression and degranulation response was mediated in an LXR-independent manner. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369608 Fri, 05 Feb 2010 00:00:00 +0100 3369608 http://www.medworm.com/index.php?rid=3369605&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000967%2Fabstract%3Frss%3Dyes Abstract: Activation gating in KcsA is elicited by changes in intracellular proton concentration. Thompson et al. identified a charge cluster around the inner gate that plays a key role in defining proton activation in KcsA. Here, through functional and spectroscopic approaches, we confirmed the role of this charge cluster and now provide a mechanism of pH-dependent gating. Channel opening is driven by a set of electrostatic interactions that include R117, E120 and E118 at the bottom of TM2 and H25 at the end of TM1. We propose that electrostatic compensation in this charge cluster stabilizes the closed conformation at neutral pH and that its disruption at low pH facilitates the transition to the open conformation by means of helix–helix repulsion. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369605 Fri, 05 Feb 2010 00:00:00 +0100 3369605 http://www.medworm.com/index.php?rid=3293937&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001043%2Fabstract%3Frss%3Dyes Abstract: The molecular mechanics property is the foundation of many characters of proteins. Based on intramolecular hydrophobic force network, the representative family character underlying a protein’s mechanics property is described by a simple two-letter scheme. The tendency of a sequence to become a member of a protein family is scored according to this mathematical representation. Remote homologs of the WW-domain family could be easily designed using such a mechanistic signature of protein homology. Experimental validation showed that nearly all artificial homologs have the representative folding and bioactivity of their assigned family. Since the molecular mechanics property is the only consideration in this study, the results indicate its possible role in the generation of new mem... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293937 Fri, 05 Feb 2010 00:00:00 +0100 3293937 http://www.medworm.com/index.php?rid=3293936&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000992%2Fabstract%3Frss%3Dyes Abstract: aP2-Cre mice have amply been used to generate conditional adipose selective inactivation of important signaling molecules. We show that the efficiency of Cre mediated recombination in adipocytes and adipose selectivity is not always guaranteed. In particular, Cre activity was found in ganglia of the peripheral nervous system (PNS), in adrenal medulla and in neurons throughout the central nervous system (CNS). Because these tissues have an important impact on adipose tissue, care should be taken when using aP2-Cre mice to define the role of the targeted genes in adipose tissue function. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293936 Fri, 05 Feb 2010 00:00:00 +0100 3293936 http://www.medworm.com/index.php?rid=3293935&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000979%2Fabstract%3Frss%3Dyes Abstract: Using conservation of synteny I show how the four thymosins expressed by teleost fish are related to the three of tetrapods, which is not evident from their protein sequences. This clarification was aided by identification of a novel thymosin of reptilians that replaces the β10 thymosin of mammals. Recent reconstruction of the ancestral vertebrate genome suggests that divergence of β-thymosins began with duplication preceding the two rounds of whole genome duplication. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293935 Fri, 05 Feb 2010 00:00:00 +0100 3293935 http://www.medworm.com/index.php?rid=3293934&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000980%2Fabstract%3Frss%3Dyes Abstract: Here we show a unique example of male infertility conferred by a gene knockout of the sperm-specific, pH-dependent SLO3 potassium channel. In striking contrast to wild-type sperm which undergo membrane hyperpolarization during capacitation, we found that SLO3 mutant sperm undergo membrane depolarization. Several defects in SLO3 mutant sperm are evident under capacitating conditions, including impaired motility, a bent “hairpin” shape, and failure to undergo the acrosome reaction (AR). The failure of AR is rescued by valinomycin which hyperpolarizes mutant sperm. Thus SLO3 is the principal potassium channel responsible for capacitation-induced hyperpolarization, and membrane hyperpolarization is crucial to the AR. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293934 Fri, 05 Feb 2010 00:00:00 +0100 3293934 http://www.medworm.com/index.php?rid=3293933&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931000092X%2Fabstract%3Frss%3Dyes Abstract: The activation of cysteine-aspartic proteases or caspases and the dynamic arrangement of cytoskeletal components are crucial during apoptosis. Here we describe the fate of Fas downstream of the FasL-induced internalization step, including formation of caspase-dependent SDS-stable Fas complexes, which is mediated by cytoskeleton integrity. We show, in particular, that following FasL treatment, the Fas lower aggregate complex can be co-immunoprecipitated with tubulin and an active form of caspase-8 and that this interaction contributes to the propagation of FasL-induced cell death. The importance of cytoskeletal components during FasL-induced apoptosis is highlighted by our detection of a pool of microtubule-associated Fas complexes. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293933 Fri, 05 Feb 2010 00:00:00 +0100 3293933 http://www.medworm.com/index.php?rid=3293906&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001031%2Fabstract%3Frss%3Dyes We present the crystal structure of the LMAN1/MCFD2 complex and relate it to patient mutations. Circular dichroism data show that the majority of the substitution mutations give rise to a disordered or severely destabilized MCFD2 protein. The few stable mutation variants are found in the binding surface of the complex leading to impaired LMAN1 binding and F5F8D.Structured summary: MINT-7557086: lman1 (uniprotkb:P49257) and mcfd2 (uniprotkb:Q8NI22) bind (MI:0407) by X-ray crystallography (MI:0114) (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293906 Fri, 05 Feb 2010 00:00:00 +0100 3293906 http://www.medworm.com/index.php?rid=3293905&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310001018%2Fabstract%3Frss%3Dyes This study provides the first evidence that MTG16b is a dual AKAP capable of binding plexins. These interactions are selective (PlexinA1 and A3 bind MTG, while PlexinB1 does not) and can be regulated by PKA-phosphorylation. Collectively, these data suggest a possible mechanism for the targeting and integration of adenosine 3′,5′-cyclic monophosphate (cAMP) and semaphorin signaling in immune cells.Structured summary: MINT-7556975: PlexinA3 (uniprotkb:P51805) physically interacts (MI:0915) with MTG 16b (uniprotkb:O75081) by anti tag coimmunoprecipitation (MI:0007)MINT-7557008: RI alpha (uniprotkb:Q9DBC7) physically interacts (MI:0915) with MTG 16b (uniprotkb:O75081) by anti bait coimmunoprecipitation (MI:0006)MINT-7556989: MTG 16b (uniprotkb:O75081) physically interacts (MI:0915) with Pl... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293905 Fri, 05 Feb 2010 00:00:00 +0100 3293905 http://www.medworm.com/index.php?rid=3293904&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000943%2Fabstract%3Frss%3Dyes Abstract: Epstein–Barr virus latent membrane protein 1 (LMP1) activates NF-κB signaling pathways through two C-terminal regions, CTAR1 and CTAR2. Previous studies have demonstrated that BS69, a multidomain cellular protein, regulates LMP1/CTAR2-mediated NF-κB activation by interfering with the complex formation between TRADD and LMP1/CTAR2. Here, we found that BS69 directly interacted with the LMP1/CTAR1 domain and regulated LMP1/CTAR1-mediated NF-κB activation and subsequent IL-6 production. Regarding the mechanisms involved, we found that BS69 directly interacted with TRAF3, a negative regulator of NF-κB activation. Furthermore, small-interfering RNA-mediated knockdown experiments revealed that TRAF3 was involved in the BS69-mediated suppression of LMP1/CTAR1-induced NF-κB activat... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293904 Fri, 05 Feb 2010 00:00:00 +0100 3293904 http://www.medworm.com/index.php?rid=3238875&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000736%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238875 Thu, 04 Feb 2010 16:23:26 +0100 3238875 http://www.medworm.com/index.php?rid=3373608&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931000089X%2Fabstract%3Frss%3Dyes Abstract: Muscle mass represents 40–50% of the human body and, in mammals, is one of the most important sites for the control of metabolism. Moreover, during catabolic conditions, muscle proteins are mobilized to sustain gluconeogenesis in the liver and to provide alternative energy substrates for organs. However, excessive protein degradation in the skeletal muscle is detrimental for the economy of the body and it can lead to death. The ubiquitin-proteasome and autophagy-lysosome systems are the major proteolytic pathways of the cell and are coordinately activated in atrophying muscles. However, the role and regulation of the autophagic pathway in skeletal muscle is still largely unknown. This review will focus on autophagy and discuss its beneficial or detrimental role for the maintena... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373608 Tue, 02 Feb 2010 00:00:00 +0100 3373608 http://www.medworm.com/index.php?rid=3369607&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000918%2Fabstract%3Frss%3Dyes Abstract: Amyloid deposits, which accumulate in numerous diseases, are the final stage of multi-step protein conformational-conversion and oligomerization processes. The underlying molecular mechanisms are not fully understood, and particularly little is known about the reverse reaction. Here we show that phosphoglycerate kinase amyloid fibrils can be converted back into native protein. We achieved recovery with 60% efficiency, which is comparable to the success rate of the unfolding-refolding studies, and the recovered enzyme was folded, stable and fully active. The key intermediate stages in the recovery process are fibril disassembly and unfolding followed by spontaneous protein folding. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3369607 Tue, 02 Feb 2010 00:00:00 +0100 3369607 http://www.medworm.com/index.php?rid=3293929&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000840%2Fabstract%3Frss%3Dyes Abstract: The crystal structure of the free form of IF1 from Mycobacterium tuberculosis has been determined at 1.47Å resolution. The structure adopts the expected OB fold and matches the high structural conservation among IF1 orthologues. In order to further explore the function of Mtb-IF1, we built a model of its interaction with the 30S ribosomal subunit based on the crystal structure of the complex from Thermus thermophilus. The model suggests that several functionally important side chain residues undergo large movements while the rest of the protein in complex shows only very limited conformational change as compared to its form in solution. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293929 Tue, 02 Feb 2010 00:00:00 +0100 3293929 http://www.medworm.com/index.php?rid=3293932&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000876%2Fabstract%3Frss%3Dyes Abstract: The crystal structure of reduced tryparedoxin peroxidase shows Cys47 close to Gln82 and Trp137 and helix formation of residues 87 to 97 whereas the NMR structure of the reduced C76S mutant adopts a different conformation similar to the oxidized protein. Circular dichroism (CD), fluorescence and NMR spectroscopy reveal that the fully active C76S mutant differs from the wildtype (WT) enzyme mainly in its reduced form both in secondary structure content and Trp137 environment. This implies that Cys76 plays a critical role for the reduced enzyme assuming different conformational states and that the catalytic triad may only be necessary as short-lived intermediate during catalysis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293932 Mon, 01 Feb 2010 00:00:00 +0100 3293932 http://www.medworm.com/index.php?rid=3293931&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000852%2Fabstract%3Frss%3Dyes Abstract: The effect of the plastoquionone (PQ) pool oxidation state on minimum chlorophyll fluorescence was studied in the green alga Chlamydomonas reinhardtii. In wild type and a mutant strain that lacks both photosystems but retains light harvesting complexes, oxygen depletion induced a rise in minimum chlorophyll fluorescence. An increase in minimum fluorescence yield is also observed when the PQ pool becomes reduced in the presence of oxygen and after application of an ionophore that collapses the transmembrane proton gradient. Together these results indicate that minimum chlorophyll fluorescence is modulated by the PQ oxidation state. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293931 Mon, 01 Feb 2010 00:00:00 +0100 3293931 http://www.medworm.com/index.php?rid=3293930&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000888%2Fabstract%3Frss%3Dyes In this study, we investigated whether protein kinase Cδ PKCδ) is involved in apoptosis induced by cationic liposomes. Tyrosine phosphorylation, nuclear localization, and cleavage of PKCδ were observed following the treatment of cells with SA-liposomes, suggesting that SA-liposomes activate PKCδ. Rottlerin, a specific inhibitor of PKCδ, inhibited ROS generation and also suppressed apoptosis. Cell surface proteoglycans may contribute to PKCδ activation by SA-liposomes. These findings suggest that PKCδ is strongly associated with apoptosis induced by SA-liposomes. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293930 Mon, 01 Feb 2010 00:00:00 +0100 3293930 http://www.medworm.com/index.php?rid=3293928&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000827%2Fabstract%3Frss%3Dyes Abstract: The tumor suppressor Kruppel-like factor 6 (KLF6) is frequently inactivated in hepatocellular carcinoma (HCC). To unearth downstream transcriptional targets of KLF6, cDNA microarray analysis of whole liver was compared between KLF6+/+ and KLF6+/− mice. Pituitary tumor transforming gene 1 (PTTG1), an oncogene, was the most up-regulated transcript in KLF6+/− liver. In human HCCs, KLF6 mRNA was significantly decreased, associated with increased PTTG1. In HepG2, KLF6 transcriptionally repressed PTTG1 by direct promoter interaction. Whereas KLF6 downregulation by siRNA increased HepG2 proliferation, siRNA to PTTG1 was anti-proliferative. PTTG1 downregulation represents a novel tumor suppressor pathway of KLF6. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293928 Fri, 29 Jan 2010 00:00:00 +0100 3293928 http://www.medworm.com/index.php?rid=3293903&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000803%2Fabstract%3Frss%3Dyes Abstract: A significant proportion of the human genome codes for transcription factors. Balanced activity of transcriptional activators and repressors is essential for normal development and differentiation. Previously we reported that a classical C2H2 zinc finger DNA binding protein ZNF652 functionally interacts with CBFA2T3 to repress transcription of genes containing ZNF652 consensus DNA binding sequence within the promoters of these target genes. Here we show that ZNF651 is a ZNF652 paralogue that shares a common DNA binding sequence with ZNF652 and represses target gene expression through the formation of a CBFA2T3–ZNF651 corepressor complex. It is suggested that CBFA2T3–ZNF651 and CBFA2T3–ZNF652 repressor complexes perform functionally similar roles in a tissue-specific manner.... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293903 Fri, 29 Jan 2010 00:00:00 +0100 3293903 http://www.medworm.com/index.php?rid=3293902&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000815%2Fabstract%3Frss%3Dyes This study provides novel insight into TM down-regulation by stress signaling pathways.Structured summary: MINT-7555703, MINT-7555712: HDAC4 (uniprotkb:P56524) physically interacts (MI:0915) with ATF-2 (uniprotkb:P15336) by anti bait coimmunoprecipitation (MI:0006) (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293902 Fri, 29 Jan 2010 00:00:00 +0100 3293902 http://www.medworm.com/index.php?rid=3293927&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000700%2Fabstract%3Frss%3Dyes Abstract: Hepatic inflammation is the key factor in non-alcoholic steatohepatitis (NASH) and promotes progression to liver damage. We recently identified dietary cholesterol as the cause of hepatic inflammation in hyperlipidemic mice. We now show that hepatic transcriptome responses are strongly dependent on cholesterol metabolism during diet-induced NASH and its inhibition by fenofibrate. Furthermore, we show that, despite doubling hepatic steatosis, pharmacological LXR activation reverses hepatic inflammation, in parallel with reversing hepatic cholesterol levels. Together, the results indicate a prominent role of cholesterol during the development, inhibition and reversal of hepatic inflammation in NASH and reveal potential new therapeutic strategies against NASH. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293927 Wed, 27 Jan 2010 00:00:00 +0100 3293927 http://www.medworm.com/index.php?rid=3293924&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000682%2Fabstract%3Frss%3Dyes Abstract: Keratin 8 and 18 are simple epithelial intermediate filament (IF) proteins, whose expression is differentiation- and tissue-specific, and is maintained during tumorigenesis. Vimentin IF is often co-expressed with keratins in cancer cells. Recently, IF have been proposed to be involved in signaling pathways regulating cell growth, death and motility. The PI3K/Akt pathway plays a pivotal role in these processes. Thus, we investigated the role of Akt (1 and 2) in regulating IF expression in different epithelial cancer cell lines. Over-expression of Akt1 increases K8/18 proteins. Akt2 up-regulates K18 and vimentin expression by an increased mRNA stability. To our knowledge, these results represent the first indication that Akt isoforms regulate IF expression and support the hypothesi... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293924 Wed, 27 Jan 2010 00:00:00 +0100 3293924 http://www.medworm.com/index.php?rid=3293901&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000694%2Fabstract%3Frss%3Dyes In this study, we used interaction proteomics to identify novel synaptic protein interactions in mouse cortical membranes under native conditions. Using immunoprecipitation, immunoblotting, and mass spectrometry, we identified a number of novel synaptic protein interactions involving soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), calcium-activated potassium channel (BKCa) alpha subunits, and dynamin-1. These novel interactions offer valuable insight into the protein–protein interaction network in intact synapses that could advance understanding of vesicle trafficking, release, and recycling.Structured summary: MINT-7543319: Snap-25 (uniprotkb:P60879) physically interacts (MI:0914) with Tubulin beta-5 chain (uniprotkb:P99024), V-type proton ATPase subunit... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293901 Wed, 27 Jan 2010 00:00:00 +0100 3293901 http://www.medworm.com/index.php?rid=3293926&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000670%2Fabstract%3Frss%3Dyes In conclusion, the effects of TNF-α on hepatic insulin resistance appear to be, at least in part, mediated by NOX3-derived ROS through a JNK pathway. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293926 Mon, 25 Jan 2010 00:00:00 +0100 3293926 http://www.medworm.com/index.php?rid=3293925&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000669%2Fabstract%3Frss%3Dyes Abstract: The small regulator SipA, interacts with the ATP-binding domain of non-bleaching sensor histidine kinase (NblS), the most conserved histidine kinase in cyanobacteria. NblS regulates photosynthesis and acclimation to a variety of environmental conditions. We show here that SipA is a highly stable protein in a wide pH range, with a thermal denaturation midpoint of 345K. Circular dichroism and 1D 1H NMR spectroscopies, as well as modelling, suggest that SipA is a β-II class protein, with short strands followed by turns and long random-coil polypeptide patches, matching the SH3 fold. The experimentally determined m-value and the heat capacity change upon thermal unfolding (ΔCp) closely agreed with the corresponding theoretical values predicted from the structural model, further sup... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293925 Mon, 25 Jan 2010 00:00:00 +0100 3293925 http://www.medworm.com/index.php?rid=3293923&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000657%2Fabstract%3Frss%3Dyes Abstract: We determined the kinetics of the reaction of human neuronal enolase and yeast enolase 1 with the slowly-reacting chromophoric substrate d-tartronate semialdehyde phosphate (TSP), each in tris (tris (hydroxymethyl) aminomethane) and another buffer at several Mg2+ concentrations, 50 or 100μM, 1mM and 30mM. All data were biphasic, and could be satisfactorily fit, assuming either two successive first-order reactions or two independent first-order reactions. Higher Mg2+ concentrations reduce the relative magnitude of the slower reaction. The results are interpreted in terms of a catalytically significant interaction between the two subunits of these enzymes. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293923 Mon, 25 Jan 2010 00:00:00 +0100 3293923 http://www.medworm.com/index.php?rid=3293922&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000645%2Fabstract%3Frss%3Dyes Abstract: The peridinin–chlorophyll a-protein (PCP) from dinoflagellates is a soluble light harvesting antenna which gathers incoming photons mainly by the carotenoid peridinin. In PCPs reconstituted with different chlorophylls, the peridinin to chlorophyll energy transfer rates are well predicted by a Förster-like theory, but only if the pigment arrangements are identical in all PCPs. We have determined the X-ray structures of PCPs reconstituted with Chlorophyll-b (Chl-b), Chlorophyll-d (Chl-d) and Bacteriochlorophyll-a (BChl-a) to resolutions ⩽2Å. In all three cases the pigment arrangements are essentially the same as in native PCP. Hydrogen bonding is not responsible for preferential incorporation of “non-native” chlorophylls over Chl-a. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293922 Mon, 25 Jan 2010 00:00:00 +0100 3293922 http://www.medworm.com/index.php?rid=3293921&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000633%2Fabstract%3Frss%3Dyes Abstract: C1qTNF-related proteins (CTRPs) are involved in diverse processes including metabolism, inflammation host defense, apoptosis, cell differentiation, autoimmunity, hibernation, and organogenesis. However, the physiological role of CTRP6 remains poorly understood. Here we demonstrate that the globular domain of CTRP6 mediates the phosphorylation and activation of the 5′-AMP-activated protein kinase (AMPK) in skeletal muscle cells. In parallel with the activation of AMPK, CTRP6 induces the phosphorylation of acetyl coenzyme A carboxylase (ACC) and fatty acid oxidation in myocytes. Thus, CTRP6 plays a role in fatty acid metabolism via the AMPK-ACC pathway. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293921 Mon, 25 Jan 2010 00:00:00 +0100 3293921 http://www.medworm.com/index.php?rid=3293920&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000591%2Fabstract%3Frss%3Dyes Abstract: Here we report that miR-26b is involved in COX-2 overexpression in desferrioxamine (DFOM)-treated carcinoma of nasopharyngeal epithelial (CNE) cells. The level of miR-26b in DFOM-treated CNE cells is inversely proportional to the expression level of the COX-2 protein. Overexpression of miR-26b in DFOM-treated CNE cells inhibits cell proliferation. A luciferase reporter gene experiment suggests that the 3′ untranslated region of COX-2 carries a binding site for miR-26b. Overexpression of miR-26b marginally reduces the levels of COX-2 protein in DFOM-treated CNE cells. Moreover, knockdown of COX-2 expression had a similar effect to overexpression of miR-26b. Taken together, these results suggest that miR-26b regulates COX-2 expression in DFOM-treated cells. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293920 Mon, 25 Jan 2010 00:00:00 +0100 3293920 http://www.medworm.com/index.php?rid=3193041&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000116%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193041 Thu, 21 Jan 2010 16:09:59 +0100 3193041 http://www.medworm.com/index.php?rid=3373609&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000268%2Fabstract%3Frss%3Dyes Abstract: Cell growth is regulated by two antagonistic processes: TOR signaling and autophagy. These processes integrate signals including growth factors, amino acids, and energy status to ensure that cell growth is appropriate to environmental conditions. Autophagy responds indirectly to the cellular milieu as a downstream inhibitory target of TOR signaling and is also directly controlled by nutrient availability, cellular energy status, and cell stress. The control of cell growth by TOR signaling and autophagy are relevant to disease, as altered regulation of either pathway results in tumorigenesis. Here we give an overview of how TOR signaling and autophagy integrate nutritional status to regulate cell growth, how these pathways are coordinately regulated, and how dysfunction of this re... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373609 Thu, 21 Jan 2010 00:00:00 +0100 3373609 http://www.medworm.com/index.php?rid=3293919&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000578%2Fabstract%3Frss%3Dyes Abstract: Mitochondrial apoptotic pathway is precisely controlled by BCL-2 family. Complex interactions of BCL-2 family proteins constitute a bistable switch of which detailed experimental and theoretical delineation remains elusive. In this paper, combined approaches were used to explore the bistability of Bax activation switch. We found that Bax activation is indeed in an ‘all-or-none’ manner. The ‘variable-delay, snap-action’ nature for Bax activation is further explored theoretically. We suggest that bistability is largely attributed to topological structure and shows considerable robustness. Therefore, our study characterizes dynamics and sensitivities in intrinsic apoptotic pathway. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293919 Thu, 21 Jan 2010 00:00:00 +0100 3293919 http://www.medworm.com/index.php?rid=3293917&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000566%2Fabstract%3Frss%3Dyes Abstract: The RNA silencing suppressor 2b protein of Cucumber mosaic virus (CMV) is difficult to produce in Escherichia coli. We compared two CMV 2b proteins that differ in their toxicity against E. coli and found that the acidic amino acid residues in the C-terminal significantly affected the toxicity and expression level of the protein in E. coli. In addition, in a DNA-binding assay, 2b had the ability to bind to DNA, and this ability was affected by the charge on the C-terminal residues of 2b. We concluded that the C-terminal residues were important for 2b’s DNA-binding ability, which may partly explain the toxicity of the protein. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293917 Thu, 21 Jan 2010 00:00:00 +0100 3293917 http://www.medworm.com/index.php?rid=3293916&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000542%2Fabstract%3Frss%3Dyes Abstract: Breitling et al. introduced a statistical technique, the rank product method, for detecting differentially regulated genes in replicated microarray experiments. The technique has achieved widespread acceptance and is now used more broadly, in such diverse fields as RNAi analysis, proteomics, and machine learning. In this note, we relate the rank product method to linear rank statistics and provide an alternative derivation of distribution theory attending the rank product method. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293916 Wed, 20 Jan 2010 00:00:00 +0100 3293916 http://www.medworm.com/index.php?rid=3373603&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000372%2Fabstract%3Frss%3Dyes Abstract: Autophagy is a bulk degradation system conserved among most eukaryotes. Recently, autophagy has been shown to mediate selective degradation of various targets such as aggregated proteins and damaged or superfluous organelles. Structural studies have uncovered the conserved specific interactions between autophagic receptors and Atg8-family proteins through WXXL-like sequences, which we term the Atg8-family interacting motif (AIM). AIM functions in various autophagic receptors such as Atg19 in the cytoplasm-to-vacuole targeting pathway, p62 and neighbor of BRCA1 gene 1 (NBR1) in autophagic degradation of protein aggregates, and Atg32 and Nix in mitophagy, and may link the target–receptor complex to autophagic membranes and/or their forming machineries. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373603 Mon, 18 Jan 2010 00:00:00 +0100 3373603 http://www.medworm.com/index.php?rid=3373601&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000384%2Fabstract%3Frss%3Dyes Abstract: Pexophagy is a selective autophagy process wherein damaged and/or superfluous peroxisomes undergo vacuolar degradation. In methylotropic yeasts, where pexophagy has been studied most extensively, this process occurs by either micro- or macropexophagy: processes analogous to micro- and macroautophagy. Recent studies have identified specific factors and illustrated mechanisms involved in pexophagy. Although mechanistically pexophagy relies heavily on the core autophagic machinery, the latest findings about the role of auxiliary pexophagy factors have highlighted specialized membrane structures required for micropexophagy, and shown how cargo selectivity is achieved and how cargo size dictates the requirement for these factors during pexophagy. These insights and additional observat... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373601 Mon, 18 Jan 2010 00:00:00 +0100 3373601 http://www.medworm.com/index.php?rid=3373595&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000396%2Fabstract%3Frss%3Dyes Abstract: Autophagy is a lysosomal degradation pathway that is essential for cellular homeostasis. Identification of more than 30 autophagy related proteins including a multi-spanning membrane protein, Atg9, has increased our understanding of the molecular mechanisms involved in autophagy. Atg9 is required for autophagy in several eukaryotic organisms although its function is unknown. Recently, we identified a novel interacting partner of mAtg9, p38 MAPK interacting protein, p38IP. We summarise recent data on the role of Atg9 trafficking in yeast and mammalian autophagy and discuss the role of p38IP and p38 MAPK in regulation of mAtg9 trafficking and autophagy. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373595 Mon, 18 Jan 2010 00:00:00 +0100 3373595 http://www.medworm.com/index.php?rid=3373591&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000360%2Fabstract%3Frss%3Dyes Abstract: Nutrient starvation induces autophagy in eukaryotic cells through inhibition of TOR (target of rapamycin), an evolutionarily-conserved protein kinase. TOR, as a central regulator of cell growth, plays a key role at the interface of the pathways that coordinately regulate the balance between cell growth and autophagy in response to nutritional status, growth factor and stress signals. Although TOR has been known as a key regulator of autophagy for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This review discusses the recent advances in understanding of the mechanism by which TOR regulates autophagy with focus on mammalian TOR (mTOR) and its regulation of the autophagy machinery. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373591 Mon, 18 Jan 2010 00:00:00 +0100 3373591 http://www.medworm.com/index.php?rid=3293918&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000402%2Fabstract%3Frss%3Dyes Abstract: The GroEL/GroES protein folding chamber is formed and dissociated by ATP binding and hydrolysis. ATP hydrolysis in the GroES-bound (cis) ring gates entry of ATP into the opposite unoccupied trans ring, which allosterically ejects cis ligands. While earlier studies suggested that hydrolysis of cis ATP is the rate-limiting step of the cycle (t½∼10s), a recent study suggested that ADP release from the cis ring may be rate-limiting (t½∼15–20s). Here we have measured ADP release using a coupled enzyme assay and observed a t½ for release of ⩽4–5s, indicating that this is not the rate-limiting step of the reaction cycle. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293918 Mon, 18 Jan 2010 00:00:00 +0100 3293918 http://www.medworm.com/index.php?rid=3293915&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000530%2Fabstract%3Frss%3Dyes Abstract: We have studied the formation of histone Hv1–DNA complexes using an acoustic biosensor and AFM imaging. Our results show that DNA and histone molecules aggregate into amorphous accumulations which form a compact rigid layer on the sensor’s surface. By measuring changes in the acoustic wave amplitude, it was possible to titrate surface bound DNA with Hv1 and discriminate between DNA molecules of different size and shape. From the kinetic analysis of real time data, Keq was found equal to 3×105M−1. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293915 Mon, 18 Jan 2010 00:00:00 +0100 3293915 http://www.medworm.com/index.php?rid=3293914&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000529%2Fabstract%3Frss%3Dyes Abstract: ClpB is a member of the AAA+ superfamily that forms a ring-shaped homohexamer. Each protomer contains two nucleotide binding domains arranged in two rings that hydrolyze ATP. We extend here previous studies on ClpB nucleotide utilization requirements by using an experimental approach that maximizes random incorporation of different subunits into the protein hexamer. Incorporation of one subunit unable to bind or hydrolyze ATP knocks down the chaperone activity, while the wt hexamer can accommodate two mutant subunits that hydrolyze ATP in only one protein ring. Four subunits seem to build the functional cooperative unit, provided that one of the protein rings contains active nucleotide binding sites. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293914 Mon, 18 Jan 2010 00:00:00 +0100 3293914 http://www.medworm.com/index.php?rid=3293913&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000517%2Fabstract%3Frss%3Dyes Abstract: We found that both wild type and Nrf3 (NF-E2-related factor 3) deficient mice are sensitive to BHT single administration exhibiting respiratory distress and considerably lose body weight following treatment. At time of sacrifice, the BHT-treated Nrf3−/− mice had lost significantly more body weight than their WT counterparts. In the lung, transcript levels of the transcription factors Nrf1, Nrf2 and Nrf3 were differentially regulated by BHT treatment. In addition, genes implicated in adipogenesis were repressed following BHT exposure in the white adipose tissue. Together, our data provide the first evidence that BHT exposure not only affects lung function but also leads to impaired adipogenesis in adipocytes. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293913 Mon, 18 Jan 2010 00:00:00 +0100 3293913 http://www.medworm.com/index.php?rid=3293912&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000463%2Fabstract%3Frss%3Dyes Abstract: Hydrogen peroxide production by the NADPH oxidase Duox1 occurs during activation of respiratory epithelial cells stimulated by purified bacterial ligands, such as lipopolysaccharide. Here, we characterize Duox activation using intact bacterial cells of several airway pathogens. We found that only Pseudomonas aeruginosa, not Burkholderia cepacia or Staphylococcus aureus, triggers H2O2 production in bronchial epithelial cells in a calcium-dependent but predominantly ATP-independent manner. Moreover, by comparing mutant Pseudomonas strains, we identify several virulence factors that participate in Duox activation, including the type-three secretion system. These data provide insight on Duox activation by mechanisms unique to P. aeruginosa. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293912 Mon, 18 Jan 2010 00:00:00 +0100 3293912 http://www.medworm.com/index.php?rid=3293911&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000451%2Fabstract%3Frss%3Dyes Abstract: Recent studies have revealed that bacteria target stem cells for long-term survival in a Drosophila model. However, in mammalian models, little is known about bacterial infection and intestinal stem cells. Our study aims at understanding bacterial regulation of the intestinal stem cell in a Salmonella colitis mouse model. We found that Salmonella activates the Wnt/β-catenin signaling pathway that is known to regulate stem cells. We identified Salmonella protein AvrA that modulates Wnt signaling including upregulating Wnt expression, modifying β-catenin, increasing total β-catenin expression, and activating Wnt/β-catenin transcriptional activity in the intestinal epithelial cells. The numbers of stem cells and proliferative cells increased in the intestine infected with Salmon... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293911 Mon, 18 Jan 2010 00:00:00 +0100 3293911 http://www.medworm.com/index.php?rid=3293910&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457931000044X%2Fabstract%3Frss%3Dyes We report here a new alternative splicing isoform of the murine CGI-58 gene, termed mCGI-58S. Sequence comparison indicates the lack of second and third exons in this cDNA variant. While the full-length protein displayed perilipin-dependent localization to lipid droplets, mCGI-58S showed a predominant cytoplasmic staining when expressed in cells. mCGI-58S was incapable of activating adipose triglyceride lipase but retained the capacity to acylate lysophosphatidic acid. Overexpression of mCGI-58S failed to promote lipid droplet turnover and loss of intracellular triacylglycerols. These results suggest that this splicing event may be involved in the regulation of lipid homeostasis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293910 Mon, 18 Jan 2010 00:00:00 +0100 3293910 http://www.medworm.com/index.php?rid=3238883&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000414%2Fabstract%3Frss%3Dyes Abstract: Chromodomain, helicase, DNA-binding protein 8 (CHD8) is an ATP-dependent chromatin remodeling enzyme that has been demonstrated to exist within a large protein complex which includes WDR5, Ash2L, and RbBP5, members of the Mixed Lineage Leukemia (MLL) histone modifying complexes. Here we show that CHD8 relocalizes to the promoter of the MLL regulated gene HOXA2 upon gene activation. Depletion of CHD8 enhances HOXA2 expression under activating conditions. Furthermore, depletion of CHD8 results in a loss of the WDR5/Ash2L/RbBP5 subcomplex, and consequently H3K4 trimethylation, at the HOXA2 promoter. These studies suggest that CHD8 alters HOXA2 gene expression and regulates the recruitment of chromatin modifying enzymes.Structured summary: MINT-7542810: CHD8 (uniprotkb:Q9HCK8) physic... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238883 Mon, 18 Jan 2010 00:00:00 +0100 3238883 http://www.medworm.com/index.php?rid=3238882&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000487%2Fabstract%3Frss%3Dyes Abstract: Oxidative stress induces apoptosis or necrosis of many cell types, which can cause tissue injury. Hydrogen peroxide (H2O2) induced apoptotic death of Jurkat cells. This effect was inhibited by overexpression of human Bcl-2, by silencing of cytochrome c, and by ablation of Bax/Bak, indicating that H2O2-induced apoptosis was mediated by the mitochondrial pathway in Jurkat cells. Treatment with H2O2 caused an increase of Noxa protein, via activating transcription factor 4-dependent accumulation of Noxa mRNA and inhibition of Noxa protein degradation. H2O2-induced apoptosis was strongly suppressed by silencing of Noxa, indicating that Noxa plays a crucial role in this form of apoptosis.Structured summary: MINT-7543162: Mcl-1 (uniprotkb:Q07820) physically interacts (MI:0914) with Bim ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238882 Mon, 18 Jan 2010 00:00:00 +0100 3238882 http://www.medworm.com/index.php?rid=3238881&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000475%2Fabstract%3Frss%3Dyes Abstract: Human holocarboxylase synthetase shows a high degree of sequence homology in the catalytic domain with bacterial biotin ligases such as Escherichia coli BirA, but differs in the length and sequence of the N-terminus. Despite several studies having been undertaken on the N-terminal region of hHCS, the role of this region remains unclear. We determined the structure of the N-terminal domain of hHCS by limited proteolysis and showed that this domain has a crucial effect on the enzymatic activity. The domain interacts not only with biotin acceptor protein, but also with the catalytic domain of hHCS, as shown by nuclear magnetic resonance (NMR) experiments. We propose that the N-terminal domain of hHCS recognizes the charged region of biotin acceptor protein, distinctly from the recog... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238881 Mon, 18 Jan 2010 00:00:00 +0100 3238881 http://www.medworm.com/index.php?rid=3238880&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000426%2Fabstract%3Frss%3Dyes This study focuses on operons from mycobacteria and the use of Mycobacterium smegmatis as an expression host. We demonstrate robust and correct stoichiometric expression of dimers to higher oligomers. The expression efficacy was found to be largely independent of the intergenic distances. The strategy was successfully extended to express mycobacterial protein complexes in Escherichia coli, showing that the operon structure of gram-positive bacteria is also functional in gram-negative bacteria. The presented strategy could become a general tool for the expression of large quantities of pure prokaryotic protein complexes for biochemical and structural studies.Structured summary: MINT-7542207: ESAT-6 (uniprotkb:Q50206) and CFP-10 (uniprotkb:O33084) bind (MI:0407) by blue native page (MI:0276)... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238880 Mon, 18 Jan 2010 00:00:00 +0100 3238880 http://www.medworm.com/index.php?rid=3293909&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000359%2Fabstract%3Frss%3Dyes Abstract: Biochemical circadian oscillation of KaiC phosphorylation, by mixing three Kai proteins and ATP, has been proven to be the central oscillator of the cyanobacterial circadian clock. In vivo, the intracellular levels of KaiB and KaiC oscillate in a circadian fashion. By scrutinizing KaiC phosphorylation rhythm in a wide range of Kai protein concentrations, KaiA and KaiB were found to be “parameter-tuning” and “state-switching” regulators of KaiC phosphorylation rhythm, respectively. Our results also suggest a possible entrainment mechanism of the cellular circadian clock with the circadian variation of intracellular levels of Kai proteins. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293909 Thu, 14 Jan 2010 00:00:00 +0100 3293909 http://www.medworm.com/index.php?rid=3293908&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000335%2Fabstract%3Frss%3Dyes Abstract: Using Arabidopsis plants transformed with a redox-sensing green fluorescent protein targeted to the cytosol (c-roGFP1), we have demonstrated, in real time, measurements of reversible changes of redox status in the cytosol of plants subjected to a gradual water-stress, followed by re-watering. Plants sensed water stress, and changed the redox potential of their cytosol to a more oxidized value after a gradually-imposed water stress. Small variations in the cytosol redox potential and ascorbate (AA) values suggest that this parameter was tightly regulated. The re-watering was paralleled by a return of water stress, redox potential and ascorbate to initial values, showing the reversibility of water stress and its consequences. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293908 Thu, 14 Jan 2010 00:00:00 +0100 3293908 http://www.medworm.com/index.php?rid=3238908&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000347%2Fabstract%3Frss%3Dyes Abstract: Translation of hepatitis C virus (HCV) genomic RNA is directed by an internal ribosome entry site (IRES) in the 5′-untranslated region (5′-UTR), and the HCV 3′-UTR enhances IRES activity. Since the HCV 3′-UTR has a unique structure among 3′-UTRs, we checked possible communication between the 5′- and the 3′-UTR of HCV during translation using chimeric reporter RNAs. We show that translation directed by the HCV IRES and by the HCV-like IRES of porcine teschovirus (PTV) which belongs to a quite distinct family of viruses (picornaviruses) or by the EMCV IRES is also enhanced by the HCV 3′-UTR or by a poly(A)-tail in different cell types. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238908 Thu, 14 Jan 2010 00:00:00 +0100 3238908 http://www.medworm.com/index.php?rid=3373607&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000256%2Fabstract%3Frss%3Dyes Abstract: Macroautophagy, a homeostatic process that shuttles cytoplasmic constituents into endosomal and lysosomal compartments, has recently been shown to deliver antigens for presentation on major histocompatibility complex (MHC) class II. Autophagy-mediated antigen processing in thymic epithelial cells has been suggested to be involved in the generation of a self-MHC restricted and self-tolerant CD4+ T cell repertoire. Furthermore, there is accumulating evidence that the up-regulation of autophagy by pattern-recognition receptor signaling represents an innate defense mechanism against intracellular pathogens. Thus, through linking pathogen breakdown with the presentation of pathogen-derived autophagy substrates on MHC class II, autophagy serves a dual function at the interface of the i... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373607 Wed, 13 Jan 2010 00:00:00 +0100 3373607 http://www.medworm.com/index.php?rid=3373599&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000244%2Fabstract%3Frss%3Dyes Abstract: Plants and plant-associated microorganisms including phytopathogens have to adapt to drastic changes in environmental conditions. Because of their immobility, plants must cope with various types of environmental stresses such as starvation, oxidative stress, drought stress, and invasion by phytopathogens during their differentiation, development, and aging processes. Here we briefly describe the early studies of plant autophagy, summarize recent studies on the molecular functions of ATG genes, and speculate on the role of autophagy in plants and phytopathogens. Autophagy regulates senescence and pathogen-induced cell death in plants, and autophagy and pexophagy play critical roles in differentiation and the invasion of host cells by phytopathogenic fungi. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373599 Wed, 13 Jan 2010 00:00:00 +0100 3373599 http://www.medworm.com/index.php?rid=3373598&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000232%2Fabstract%3Frss%3Dyes Abstract: Drosophila has been shown to be a powerful model to study autophagy, whose regulation involves a core machinery consisting of Atg proteins and upstream signaling regulators similar to those in yeast and mammals. The conserved role in degrading proteins and organelles gives autophagy an important function in coordinating several cellular processes as well as in a number of pathological conditions. This review summarizes key studies in Drosophila autophagy research and discusses potential questions that may lead to better understanding of the roles and regulation of autophagy in higher eukaryotes. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373598 Wed, 13 Jan 2010 00:00:00 +0100 3373598 http://www.medworm.com/index.php?rid=3373593&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000293%2Fabstract%3Frss%3Dyes Abstract: The simple phosphoinositide phosphatidylinositol 3-phosphate (PI(3)P) has been known to have important functions in endocytic and phagocytic traffic, and to be required for the autophagic pathway. In all of these settings, PI(3)P appears to create platforms that serve to recruit specific effectors for membrane trafficking events. In autophagy, PI(3)P may form the platform for autophagosome biogenesis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373593 Wed, 13 Jan 2010 00:00:00 +0100 3373593 http://www.medworm.com/index.php?rid=3293907&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000219%2Fabstract%3Frss%3Dyes Abstract: NADH:ubiquinone oxidoreductase (complex I) is the entry enzyme of mitochondrial oxidative phosphorylation. To obtain the structural information on inhibitor/quinone binding sites, we synthesized [3H]benzophenone-asimicin ([3H]BPA), a photoaffinity analogue of asimicin, which belongs to the acetogenin family known as the most potent complex I inhibitor. We found that [3H]BPA was photo-crosslinked to ND2, ND1 and ND5 subunits, by the three dimensional separation (blue-native/doubled SDS–PAGE) of [3H]BPA-treated bovine heart submitochondrial particles. The cross-linking was blocked by rotenone. This is the first finding that ND2 was photo-crosslinked with a potent complex I inhibitor, suggesting its involvement in the inhibitor/quinone-binding. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3293907 Wed, 13 Jan 2010 00:00:00 +0100 3293907 http://www.medworm.com/index.php?rid=3238907&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000220%2Fabstract%3Frss%3Dyes Abstract: Gangliosides are targets for a variety of pathologically relevant proteins, including amyloid β (Aβ), an important component implicated in Alzheimer’s disease (AD). To provide a structural basis for this pathogenic interaction associated with AD, we conducted NMR analyses of the Aβ interactions with gangliosides using lyso-GM1 micelles as a model system. Our NMR data revealed that the sugar–lipid interface is primarily perturbed upon binding of Aβ to the micelles, underscoring the importance of the inner part of the ganglioside cluster for accommodating Aβ in comparison with the outer carbohydrate branches that provide microbial toxin- and virus-binding sites. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238907 Wed, 13 Jan 2010 00:00:00 +0100 3238907 http://www.medworm.com/index.php?rid=3238906&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000062%2Fabstract%3Frss%3Dyes Abstract: Crystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an Nε-methyl lysine histone demethylase associated with mental retardation and cleft lip/palate, reveals a double-stranded β-helix fold with conserved Fe(II) and cosubstrate binding sites typical of the 2-oxoglutarate dependent oxygenases. The PHF8 active site is highly conserved with those of the FBXL10/11demethylases, which are also selective for the di-/mono-methylated lysine states, but differs from that of the JMJD2 demethylases which are selective for tri-/di-methylated states. The results rationalize the lack of activity for the clinically observed F279S PHF8 variant and they will help to identify inhibitors selective for specific Nε-methyl lysine demethylase subfamilies. (Source: FEBS Let... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238906 Mon, 11 Jan 2010 00:00:00 +0100 3238906 http://www.medworm.com/index.php?rid=3238905&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000050%2Fabstract%3Frss%3Dyes Abstract: Recent studies have indicated that acetylcholine (ACh) plays a vital role in various tissues, while the role of ACh in bone metabolism remains unclear. Here we demonstrated that ACh induced cell proliferation and reduced alkaline phosphatase (ALP) activity via nicotinic (nAChRs) and muscarinic acetylcholine receptors (mAChRs) in osteoblasts. We detected mRNA expression of several nAChRs and mAChRs. Furthermore, we showed that cholinergic components were up-regulated and subunits/subtypes of acetylcholine receptors altered during osteoblast differentiation. To our knowledge, this is the first report demonstrating that osteoblasts express specific acetylcholine receptors and cholinergic components and that ACh plays a possible role in regulating the proliferation and differentiatio... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238905 Mon, 11 Jan 2010 00:00:00 +0100 3238905 http://www.medworm.com/index.php?rid=3238904&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000037%2Fabstract%3Frss%3Dyes In this study, we examined the miRNA profile of HK-2 cells and found that high glucose/TGF-β1 induced significant down-regulation of miR-29a. We then showed that miR-29a negatively regulated collagen IV by directly targeting the 3′UTRs of col4a1 and col4a2. These results suggest that miR-29a acts as a repressor to fine-tune collagen expression and that the reduction of miR-29a caused by high glucose may increase the risk of excess collagen deposition in PTCs. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238904 Mon, 11 Jan 2010 00:00:00 +0100 3238904 http://www.medworm.com/index.php?rid=3238903&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000049%2Fabstract%3Frss%3Dyes Abstract: Estrogen plays important roles in the reproductive behavior of animals. In the present study, we found that the Grin2d gene of mouse possessed half-sites of the estrogen-responsive element (ERE) in the 3′-untranslated region (UTR). Quantitative PCR analysis showed that the reduced Grin2d mRNA expression in the hypothalamus of the ovariectomized mice was restored by estrogen administration. Downregulation of Grin2d mRNA expression was also detected in the hypothalamus of estrogen receptor alpha-knockout female mice. Moreover, estrogen-induced lordosis response was decreased in Grin2d-knockout mice. These results suggest that estrogen regulates lordosis behavior through the regulation of Grin2d expression in the hypothalamus of female mice. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238903 Mon, 11 Jan 2010 00:00:00 +0100 3238903 http://www.medworm.com/index.php?rid=3238902&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000025%2Fabstract%3Frss%3Dyes Abstract: Bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9 (GDF-9) are oocyte-secreted factors that play essential roles in human folliculogenesis and ovulation. Their bioactivity is tightly regulated through phosphorylation, likely to occur within the Golgi apparatus of the secretory pathway. Here we show that Golgi apparatus casein kinase (G-CK) catalyzes the phosphorylation of rhBMP-15 and rhGDF-9. rhBMP-15, in particular, is an excellent substrate for G-CK. In each protein a single residue is phosphorylated by G-CK, corresponding to the serine residue at the sixth position of the mature region of both rhBMP-15 and rhGDF-9, whose phosphorylation is required for biological activity. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238902 Mon, 11 Jan 2010 00:00:00 +0100 3238902 http://www.medworm.com/index.php?rid=3238901&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000086%2Fabstract%3Frss%3Dyes Abstract: Human transforming growth factor-β receptor type 2 (TGFβR2) mRNA harboring a premature translation termination codon (PTC) generated by frameshift mutation is targeted for nonsense-mediated translational repression (NMTR), rather than nonsense-mediated mRNA decay (NMD). Here we show that exon junction complex (EJC) downstream of a PTC plays an inhibitory role in translation of TGFβR2 mRNA. Translational repression by core EJC components occurs after formation of 80S ribosome complex, which is demonstrated using different types of internal ribosome entry sites (IRESes). Our findings implicate EJCs or core EJC components as negative regulators of translation. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238901 Mon, 11 Jan 2010 00:00:00 +0100 3238901 http://www.medworm.com/index.php?rid=3238898&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579310000074%2Fabstract%3Frss%3Dyes Abstract: Many proteins fibrillate at low pH despite a high population of charged side chains. Therefore exchange of protons between the fibrillating peptide and its surroundings may play an important role in fibrillation. Here, we use isothermal titration calorimetry to measure exchange of protons between buffer and the peptide hormone glucagon during fibrillation. Glucagon absorbs or releases protons to an extent which allows it to attain a net charge of zero in the fibrillar state, both at acidic and basic pH. Similar results are obtained for lysozyme. This suggests that side chain pKa values change dramatically in the fibrillar state. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238898 Mon, 11 Jan 2010 00:00:00 +0100 3238898 http://www.medworm.com/index.php?rid=3238877&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010758%2Fabstract%3Frss%3Dyes Abstract: The length of the isoprenoid-side chain in ubiquinone, an essential component of the electron transport chain, is defined by poly-prenyl diphosphate synthase, which comprises either homomers (e.g., IspB in Escherichia coli) or heteromers (e.g., decaprenyl diphosphate synthase (Dps1) and D-less polyprenyl diphosphate synthase (Dlp1) in Schizosaccharomyces pombe and in humans). We found that expression of either dlp1 or dps1 recovered the thermo-sensitive growth of an E. coli ispBR321A mutant and restored IspB activity and production of Coenzyme Q-8. IspB interacted with Dlp1 (or Dps1), forming a high-molecular weight complex that stabilized IspB, leading to full functionality.Structured summary:: MINT-7385426:Dlp1 (uniprotkb:Q86YH6) and IspB (uniprotkb:P0AD57) physically interact ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238877 Mon, 04 Jan 2010 00:00:00 +0100 3238877 http://www.medworm.com/index.php?rid=3238900&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010941%2Fabstract%3Frss%3Dyes In this report, we demonstrate a novel class of RF3 mutations specifically defective in the tRNA drop-off reaction. These mutations suggest differential molecular pathways closely related to the guanine nucleotide modes of RF3. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238900 Tue, 29 Dec 2009 00:00:00 +0100 3238900 http://www.medworm.com/index.php?rid=3238899&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010928%2Fabstract%3Frss%3Dyes Abstract: The glucagon receptor antagonist BI-32169, recently isolated from Streptomyces sp., was described as a bicyclic peptide, although its primary structure comprises conserved elements of class I and class II lasso peptides. Tandem mass spectrometric and nuclear magnetic resonance spectroscopic studies revealed that BI-32169 is a lasso-structured peptide constituting the new class III of lasso peptides. The determined lasso fold opens new avenues to improve the promising biological activity of BI-32169. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238899 Tue, 29 Dec 2009 00:00:00 +0100 3238899 http://www.medworm.com/index.php?rid=3238879&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010977%2Fabstract%3Frss%3Dyes Abstract: RKIP was first identified as an inhibitor of the Raf-MEK-ERK signaling pathway. RKIP was also found to play an important role in the NF-κB pathway. Genetic and biochemical studies demonstrated that RKIP functioned as a scaffold protein facilitating the phosphorylation of IκB by upstream kinases. However, contrary to what one would expect of a scaffold protein, our results show that RKIP has an overall inhibitory effect on the NF-κB transcriptional activities. Since NF-κB target gene expression is subject to negative regulation involving the optimal induction of negative regulators, our data support a hypothesis that RKIP inhibits NF-κB activity via the auto-regulatory feedback loop by rapidly inducing the expression and synthesis of inhibitors of NF-κB activation.Structured... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238879 Tue, 29 Dec 2009 00:00:00 +0100 3238879 http://www.medworm.com/index.php?rid=3238878&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010965%2Fabstract%3Frss%3Dyes Abstract: Bone morphogenetic protein-1 (BMP-1)/tolloid proteinases are fundamental to regulating dorsal ventral patterning and extracellular matrix deposition. In mammals there are four proteinases, the splice variants BMP-1 and mammalian tolloid (mTLD), and tolloid like-1 and -2 (TLL-1/2). BMP-1 has the highest catalytic activity and lacks three non-catalytic domains. We demonstrate that TLL-1, which has intermediate activity, forms a calcium-ion dependent dimer with monomers stacked side-by-side. In contrast, truncated TLL-1 molecules having the same shorter structure as BMP-1 are monomers and have improved activity towards their substrate chordin. The increased activity exceeds not only that of full-length TLL-1 but also BMP-1.Structured summary: MINT-7386098: BMP-1 (uniprotkb:P13497) c... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238878 Tue, 29 Dec 2009 00:00:00 +0100 3238878 http://www.medworm.com/index.php?rid=3373605&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457930901093X%2Fabstract%3Frss%3Dyes Abstract: The ubiquitin proteasome system (UPS) and macroautophagy (hereafter called autophagy) were, for a long time, regarded as independent degradative pathways with few or no points of interaction. This view started to change recently, in the light of findings that have suggested that ubiquitylation can target substrates for degradation via both pathways. Moreover, perturbations in the flux through either pathway have been reported to affect the activity of the other system, and a number of mechanisms have been proposed to rationalise the link between the UPS and autophagy. Here we critically review these findings and outline some outstanding issues that still await clarification. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373605 Mon, 28 Dec 2009 00:00:00 +0100 3373605 http://www.medworm.com/index.php?rid=3238897&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010904%2Fabstract%3Frss%3Dyes Abstract: Immunoglobulin E (IgE) production is induced by interleukin (IL)-4 signaling mediated by type I IL-4 receptor (IL-4R) in B cells. We found that flavones inhibited IL-4-induced ε germline transcription which is essential for IgE class switching, and the phosphorylation of signal transducer and activator of transcription 6, janus kinase 3, and IL-4Rα, whereas IL-4 signaling mediated through type II IL-4R was unaffected by flavones. Furthermore, flavones reduced the expression of common gamma chain, a characteristic constituent subunit of type I IL-4R, suggesting that flavones suppress type I IL-4R signaling. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238897 Mon, 28 Dec 2009 00:00:00 +0100 3238897 http://www.medworm.com/index.php?rid=3373596&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010837%2Fabstract%3Frss%3Dyes Abstract: Autophagy is a non-selective degradation process in eukaryotic cells. The genome sequence of the fission yeast Schizosaccharomyces pombe has revealed that many of the genes required for autophagy are common between the fission yeast and budding yeast, suggesting that the basic machinery of autophagy is conserved between these species. Autophagy in fission yeast is specifically induced by nitrogen starvation based on monitoring a GFP–Atg8p marker. Upon nitrogen starvation, fission yeast cells exit the vegetative cell cycle and initiate sexual differentiation to produce spores. Most of the nitrogen used for de novo protein synthesis during sporulation derives from the autophagic protein degradation system. This review focuses on the recent advances in the role of autophagy in fis... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373596 Fri, 25 Dec 2009 00:00:00 +0100 3373596 http://www.medworm.com/index.php?rid=3238896&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010874%2Fabstract%3Frss%3Dyes Abstract: Pigmentation in avian eggshells appears to be associated with shell strength, temperature regulation, and camouflage. The pigments found in eggshells are mainly porphyrins, which have been utilized therapeutically as photosensitizers. Here, we examined the photoinactivation of gram-positive (Staphylococcus aureus, Bacillus cereus) and gram-negative bacteria (Escherichia coli, Salmonella enteritidis) by hen eggshells and their pigments. The results indicated that eggshells have a light-dependent antimicrobial activity against gram-positive, but not gram-negative, bacteria. Our results indicate the possibility that the natural pigments used therapeutically have evolved in nature as a defence system. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238896 Fri, 25 Dec 2009 00:00:00 +0100 3238896 http://www.medworm.com/index.php?rid=3238895&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010862%2Fabstract%3Frss%3Dyes In this study, we found that the second phosphotyrosine interaction domain (PI2) of FE65 mediated its trans-accumulation in the nuclear matrix of osmotically stressed cells. The carboxyl-terminal half of FE65, which contains the PI2 domain, failed to stabilize p53, suggesting that the amino-terminal half of the protein plays an important role in the stabilization of p53 in osmotically stressed cells. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238895 Fri, 25 Dec 2009 00:00:00 +0100 3238895 http://www.medworm.com/index.php?rid=3238890&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010916%2Fabstract%3Frss%3Dyes Abstract: Prokaryotic pathogens have developed specialized mechanisms for efficient uptake of ferrous iron (Fe2+) from the host. In Legionella pneumophila, the causative agent of Legionnaires’ disease, the transmembrane GTPase FeoB plays a key role in Fe2+ acquisition and virulence. FeoB consists of a membrane-embedded core and an N-terminal, cytosolic region (NFeoB). Here, we report the crystal structure of NFeoB from L. pneumophila, revealing a monomeric protein comprising two separate domains with GTPase and guanine-nucleotide dissociation inhibitor (GDI) functions. The GDI domain displays a novel fold, whereas the overall structure of the GTPase domain resembles that of known G domains but is in the rarely observed nucleotide-free state. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238890 Fri, 25 Dec 2009 00:00:00 +0100 3238890 http://www.medworm.com/index.php?rid=3373610&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010801%2Fabstract%3Frss%3Dyes Abstract: Autophagy, or cellular self-digestion, is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance. Nonetheless, genetic evidence supports that autophagy functions as a tumor suppressor mechanism. Hence, the precise role of autophagy during cancer progression and treatment is both tissue and context dependent. Here, we discuss our current understanding of the biological functions of autophagy during cancer development, overview how autophagy is regulated by cancer-associated signaling pathways, and review how autophagy inhibition is being exploited to improve clinical outcomes. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373610 Thu, 24 Dec 2009 00:00:00 +0100 3373610 http://www.medworm.com/index.php?rid=3238894&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010771%2Fabstract%3Frss%3Dyes Abstract: The PsbS protein is a critical component in the regulation of non-photochemical quenching (NPQ) in higher plant photosynthesis. Electron microscopy and image analysis of grana membrane fragments from wild type and mutant Arabidopsis plants showed that the semi-crystalline domains of photosystem II supercomplexes were identical in the presence and absence of PsbS. However, the frequency of the domains containing crystalline arrays was increased in the absence of PsbS. Conversely, there was a complete absence of such arrays in the membranes of plants containing elevated amounts of this protein. It is proposed that PsbS controls the macro-organisation of the grana membrane, providing an explanation of its role in NPQ. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238894 Thu, 24 Dec 2009 00:00:00 +0100 3238894 http://www.medworm.com/index.php?rid=3373606&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010710%2Fabstract%3Frss%3Dyes Abstract: Chaperone-mediated autophagy (CMA) is a lysosomal pathway that participates in the degradation of cytosolic proteins. CMA is activated by starvation and in response to stressors that result in protein damage. The selectivity intrinsic to CMA allows for removal of damaged proteins without disturbing nearby functional ones. CMA works in a coordinated manner with other autophagic pathways, which can compensate for each other. Interest in CMA has recently grown because of the connections established between this autophagic pathway and human pathologies. Here we review the unique properties of CMA compared to other autophagic pathways and its relevance in health and disease. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3373606 Tue, 22 Dec 2009 00:00:00 +0100 3373606 http://www.medworm.com/index.php?rid=3238893&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457930901076X%2Fabstract%3Frss%3Dyes Abstract: Neuronal gene transcription is regulated by both transcriptional activators and repressors. While the roles of transactivators in retinal photoreceptor development have been well characterized, the roles of repressors have been poorly understood. We isolated Panky/Ankrd33, a gene encoding an ankyrin repeat-containing protein. Panky-A was specifically expressed in retinal photoreceptors and the pineal gland, and its expression was directly up-regulated by the CRX transcription factor. Subcellular localization of PANKY-A was observed in the nucleus and cytoplasm. Additionally, transactivation analysis suggested that PANKY-A is a transcriptional cofactor that suppresses CRX-activated photoreceptor genes. Furthermore, we found by an electrophoretic mobility shift assay that PANKY inh... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238893 Tue, 22 Dec 2009 00:00:00 +0100 3238893 http://www.medworm.com/index.php?rid=3238892&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010746%2Fabstract%3Frss%3Dyes This study investigated the role of mechanical stimulation in the regulation of eIF2α and cell death. Mechanical stimulation was applied to mouse ulnae, MC3T3 cells, and mesenchymal stem cells. The results demonstrate that mechanical stimulation reduces phosphorylation of eIF2α through inactivation of Perk. Furthermore, flow pre-treatment reduces thapsigargin-induced cell mortality through suppression of phosphorylation of Perk. However, H2O2-driven cell mortality, which is not mediated by Perk, is not suppressed by mechanical stimulation. Taken together, our observations suggest a pro-survival role of mechanical stimulation in Perk-mediated stress responses. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238892 Tue, 22 Dec 2009 00:00:00 +0100 3238892 http://www.medworm.com/index.php?rid=3238891&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010722%2Fabstract%3Frss%3Dyes Abstract: Combined bisulfite restriction analysis (COBRA) is one of the most commonly used methylation quantification methods. However, it focuses on relatively few restriction enzymes. Here, we present Methyl-Typing, a web-based software that provides restriction enzyme mining data for methyl-cytosine-containing sequences following bisulfite-conversion. Gene names, accession numbers, sequences, PCR primers, and file upload are accessible for input. Promoter sequences and restriction enzymes for CpG- and GpC-containing recognition sites are retrieved. Four representative enzymes were tested successfully by COBRA on the experimental work. Therefore, the Methyl-Typing tool provides a comprehensive COBRA-restriction enzyme mining. It is freely available at http://bio.kuas.edu.tw/methyl-typing... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238891 Tue, 22 Dec 2009 00:00:00 +0100 3238891 http://www.medworm.com/index.php?rid=3238889&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010734%2Fabstract%3Frss%3Dyes Abstract: The stress-activated kinase Hog1p mediates arsenic tolerance by decreasing arsenite influx through the aquaglyceroporin Fps1p in Saccharomyces cerevisiae. Unexpectedly, we found that overexpression of FPS1 increased arsenite tolerance suggesting a physiological role of Fps1p in arsenic detoxification. Consistently, during arsenite treatment transcription of FPS1 gene was strongly upregulated, while Fps1p was not degraded and remained localized to the plasma membrane. Moreover, deletion of FPS1 gene resulted in arsenate sensitivity. Finally, transport experiments revealed that Fps1p in concert with the arsenite transporter Acr3p mediates arsenite efflux. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238889 Tue, 22 Dec 2009 00:00:00 +0100 3238889 http://www.medworm.com/index.php?rid=3238888&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010692%2Fabstract%3Frss%3Dyes Abstract: Hepcidin is a small acute phase peptide that regulates iron absorption. It is induced by inflammation and infection, but is repressed by anaemia and hypoxia. Here we further reveal that hepcidin transcription also involves interactions between functional metal response elements (MREs) in its promoter, and the MRE-binding transcription factor-1. Analysis of hepcidin mRNA and protein levels in hepatoma cells suggests that its expression may be regulated by divalent metal ions, with zinc inducing maximal effects on hepcidin levels. These data suggest that this peptide may be a pleiotropic sensor of divalent metals, some of which are xenobiotic environmental toxins. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238888 Tue, 22 Dec 2009 00:00:00 +0100 3238888 http://www.medworm.com/index.php?rid=3238887&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010709%2Fabstract%3Frss%3Dyes Abstract: The C-terminal residues 98–104 are important for structure stability of subunit H of A1AO ATP synthases as well as its interaction with subunit A. Here we determined the structure of the segment H85–104 of H from Methanocaldococcus jannaschii, showing a helix between residues Lys90 to Glu100 and flexible tails at both ends. The helix–helix arrangement in the C-terminus was investigated by exchange of hydrophobic residues to single cysteine in mutants of the entire subunit H (HI93C, HL96C and HL98C). Together with the surface charge distribution of H85–104, these results shine light into the A–H assembly of this enzyme. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238887 Tue, 22 Dec 2009 00:00:00 +0100 3238887 http://www.medworm.com/index.php?rid=3238876&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010679%2Fabstract%3Frss%3Dyes Abstract: We previously reported that gentamicin (GM) specifically binds to heat-shock protein with subunit molecular masses of 70kDa (HSP70). In the present study, we have investigated the effects of GM binding on HSP70-assisted protein folding in vitro. The C-terminal, and not the N-terminal of HSP70 was found to bind to GM. GM significantly suppressed refolding of firefly luciferase in the presence of HSP70 and HSP40, although the ATPase activity of HSP70 was unaffected by GM. A surface plasmon resonance analysis revealed that GM specifically interferes with the binding of HSP70 to a model peptide that mimics the exposed hydrophobic surface of the folding intermediates. These results indicated that GM inhibits the chaperone activity of HSP70 and may suppress protein folding via inhibiti... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238876 Tue, 22 Dec 2009 00:00:00 +0100 3238876 http://www.medworm.com/index.php?rid=3193043&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010680%2Fabstract%3Frss%3Dyes Abstract: Apoptosis is a form of programmed cell death crucial for development, homeostasis, immunity, spermatogenesis, and prevention of cancer. Positive selection acting on mammalian apoptosis related genes targets protein interfaces that interact with pathogens and also elements of signaling complexes. Selection appears primarily to be driven by the immune/defense related function of these genes. Moreover, competitive interactions could be driving positive selection among sperm cells, as well as the need for protection against female anti-sperm immune responses. Trade-offs in fitness are expected out of these selective pressures, which could explain the involvement of these genes in various diseases, including cancer. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193043 Tue, 22 Dec 2009 00:00:00 +0100 3193043 http://www.medworm.com/index.php?rid=3238886&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010655%2Fabstract%3Frss%3Dyes In this study, we showed that curcumin decreases HCV gene expression via suppression of the Akt-SREBP-1 activation, not by NF-κB pathway. The combination of curcumin and IFNα exerted profound inhibitory effects on HCV replication. Collectively, our results indicate that curcumin can suppress HCV replication in vitro and may be potentially useful as novel anti-HCV reagents. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238886 Thu, 17 Dec 2009 00:00:00 +0100 3238886 http://www.medworm.com/index.php?rid=3238885&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010643%2Fabstract%3Frss%3Dyes Abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a liver-secreted plasma enzyme, restricts hepatic uptake of low-density lipoprotein (LDL) cholesterol by promoting the degradation of LDL receptors (LDLR). PCSK9 and LDLR are also expressed in insulin-producing pancreatic islet β cells, possibly affecting the function of these cells. Here we show that, compared to control mice, PCSK9-null male mice over 4months of age carried more LDLR and less insulin in their pancreas; they were hypoinsulinemic, hyperglycemic and glucose-intolerant; their islets exhibited signs of malformation, apoptosis and inflammation. Collectively, these observations suggest that PCSK9 may be necessary for the normal function of pancreatic islets. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238885 Thu, 17 Dec 2009 00:00:00 +0100 3238885 http://www.medworm.com/index.php?rid=3238884&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010667%2Fabstract%3Frss%3Dyes Abstract: O-GlcNAcylation is an essential posttranslational modification in metazoa. Modulation of O-GlcNAc levels with small molecule inhibitors of O-GlcNAc hydrolase (OGA) is a useful strategy to probe the role of this modification in a range of cellular processes. Here we report the discovery of novel, low molecular weight and drug-like O-GlcNAcase inhibitor scaffolds by high-throughput screening. Kinetic and X-ray crystallographic analyses of the binding modes with human/bacterial O-GlcNAcases identify some of these as competitive inhibitors. Comparative kinetic experiments with the mechanistically related human lysosomal hexosaminidases reveal that three of the inhibitor scaffolds show selectivity towards human OGA. These scaffolds provide attractive starting points for the developmen... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3238884 Thu, 17 Dec 2009 00:00:00 +0100 3238884 http://www.medworm.com/index.php?rid=3193042&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010631%2Fabstract%3Frss%3Dyes FEBS Letters readers may know that our Spotlight series is dedicated to the members of our Editorial Board, in the attempt to reveal the scientific expertise the journal relies upon, but also to familiarize with the people that lie behind our pages. In this particular issue, we chose to turn our spotlight onto an honorary member of FEBS Letters, who had a central role in contributing to the journal’s success. Professor Giorgio Semenza was Managing Editor of FEBS Letters between 1985 and 1999, succeeding the founder of the journal, Prof. S.P. Datta, the other Honorary Chairman of the Editorial Board. During his early career, Giorgio Semenza contributed to the initial development of protein chromatography in Prof. A. Tiselius’ laboratory, and later concentrated on structural and function... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193042 Wed, 16 Dec 2009 00:00:00 +0100 3193042 http://www.medworm.com/index.php?rid=3084302&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010175%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3084302 Mon, 14 Dec 2009 15:50:41 +0100 3084302 http://www.medworm.com/index.php?rid=3193070&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457930901062X%2Fabstract%3Frss%3Dyes This study contains the first experimental evidence that the bi-nuclear part of the H-cluster is assembled in HydF. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193070 Mon, 14 Dec 2009 00:00:00 +0100 3193070 http://www.medworm.com/index.php?rid=3193069&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010606%2Fabstract%3Frss%3Dyes We describe a novel and selective small molecule inhibitor of PKD, bipyridyl PKD inhibitor (BPKDi). BPKDi blocks signal-dependent phosphorylation and nuclear export of class IIa HDACs in cardiomyocytes and concomitantly suppresses hypertrophy of these cells. These studies define PKD as a principal cardiac class IIa HDAC kinase. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193069 Mon, 14 Dec 2009 00:00:00 +0100 3193069 http://www.medworm.com/index.php?rid=3193068&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010588%2Fabstract%3Frss%3Dyes In this report, we describe the structural changes undergone by GAPDH at physiological pH and temperature conditions right from its interaction with acidic membranes until the amyloid fibril is formed. According to our results, the GAPDH-membrane binding induces a β-structuring process along with a loss of quaternary structure in the enzyme. In this way, experimental evidences on the initial steps of GAPDH amyloid fibrils formation pathway are provided. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193068 Mon, 14 Dec 2009 00:00:00 +0100 3193068 http://www.medworm.com/index.php?rid=3193067&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010576%2Fabstract%3Frss%3Dyes We report here that inducible overexpression of the transcription factor Sharp-1 results in an S and G2/M cell cycle arrest, concomitant with the upregulation of Brca1 and GADD45α expression. In addition, we show that endogenous Sharp-1 mRNA is increased by DNA-damaging agents. Consistently, Sharp-1 overexpressing cells exhibit reduced apoptosis in response to chemotherapeutic drugs along with lower p53 expression and activity. Our studies identify a novel function for Sharp-1 in cell cycle arrest and DNA damage-induced apoptosis. Inappropriate Sharp-1 expression may therefore be associated with tumorigenesis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193067 Mon, 14 Dec 2009 00:00:00 +0100 3193067 http://www.medworm.com/index.php?rid=3193066&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS001457930901059X%2Fabstract%3Frss%3Dyes Abstract: Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid in neuronal cell membranes. We hypothesize that DHA induces a decrease in neuronal cell death through reduced ZnT3 expression and zinc uptake. Exposure of M17 cells to DHA-deficient medium increased the levels of active caspase-3, relative to levels in DHA-replete cells, confirming the adverse effects of DHA deficiency in promoting neuronal cell death. In DHA-treated M17 cells, zinc uptake was 65% less and ZnT3 mRNA and protein levels were reduced in comparison with DHA-depleted cells. We propose that the neuroprotective function of DHA is exerted through a reduction in cellular zinc levels that in turn inhibits apoptosis. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193066 Mon, 14 Dec 2009 00:00:00 +0100 3193066 http://www.medworm.com/index.php?rid=3193049&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010552%2Fabstract%3Frss%3Dyes This study demonstrates that the catalytically active T49M and I51N mutants undergo accelerated degradation, which results in their reduced cellular levels. Inhibition of proteasome leads to significant accumulation of ubiquitylated T49M and I51N. Furthermore, the degree of ubiquitylation strongly correlates with the half-lives of the proteins. These results suggest that the accelerated degradation of RDH12 mutants by the ubiquitin-proteasome system contributes to the pathophysiology and phenotypic variability associated with mutations in the RDH12 gene.Structured summary: MINT-7383581, MINT-7383598: RDH12 (uniprotkb:Q96NR8) physically interacts (MI:0915) with ubiquitin (uniprotkb:P62988) by anti tag coimmunoprecipitation (MI:0007) (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193049 Mon, 14 Dec 2009 00:00:00 +0100 3193049 http://www.medworm.com/index.php?rid=3193048&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010618%2Fabstract%3Frss%3Dyes Abstract: In naive T cells, Lck exerts a negative control on the ERK/MAPK pathway. We show that c-mip (c-maf inducing protein) interacts with the p85 subunit of PI3 kinase and inactivates Lck, which results in Erk1/2 and p38 MAPK activation. This effect is not enough to activate AP1 given the inability of ERK to migrate into the nucleus and to transactivate its target genes. We demonstrate that c-mip interacts with Dip1 and upregulates DAPK, which blocks the nuclear translocation of ERK1/2. This dual effect of c-mip is unique and might represent a potential mechanism to prevent the development of an immune response.Structured summary: MINT-7383650: p85 (uniprotkb:P27986) physically interacts (MI:0915) with c-Mip (uniprotkb:Q8IY22) by anti bait coimmunoprecipitation (MI:0006)MINT-7383661: c... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193048 Mon, 14 Dec 2009 00:00:00 +0100 3193048 http://www.medworm.com/index.php?rid=3078532&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010321%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3078532 Fri, 11 Dec 2009 15:42:36 +0100 3078532 http://www.medworm.com/index.php?rid=3078531&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010059%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3078531 Fri, 11 Dec 2009 15:42:36 +0100 3078531 http://www.medworm.com/index.php?rid=3193064&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010540%2Fabstract%3Frss%3Dyes Abstract: We found that Tyr-Leu (YL) dose-dependently exhibits potent anxiolytic-like activity (0.1–1mg/kg, i.p.) comparable to diazepam in the elevated plus-maze test in mice. YL was orally active (0.3–3mg/kg). A retro-sequence peptide or a mixture of Tyr and Leu was inactive. The anxiolytic-like activity of YL was inhibited by antagonists for serotonin 5-HT1A, dopamine D1 and GABAA receptors; however, YL had no affinity for them. We also determined the order of their activation is 5-HT1A, D1 and GABAA receptors using selective agonists and antagonists. Taken together, YL may exhibit anxiolytic-like activity via activation of 5-HT1A, D1 and GABAA receptors. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193064 Fri, 11 Dec 2009 00:00:00 +0100 3193064 http://www.medworm.com/index.php?rid=3193063&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010539%2Fabstract%3Frss%3Dyes This study describes the first application of unlocked nucleic acid (UNA)-modified small interfering RNAs (siRNAs) directed against a medically relevant target, the coxsackievirus B3. We systematically analyzed the impact of different siRNA modification patterns and observed good compatibility of the introduction of UNA with the maintenance of high antiviral activity. Additionally, the polarity of an siRNA was successfully reversed by modulating the relative stability of the termini with locked nucleic acid (LNA) and UNA as shown in a reporter assay. The potency of the reversed siRNA against the full-length target was, however, too low to inhibit the infectious virus. Altogether, combined modification of siRNAs with LNA und UNA provides a promising approach to alter and improve properties ... FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193063 Fri, 11 Dec 2009 00:00:00 +0100 3193063 http://www.medworm.com/index.php?rid=3070489&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309009454%2Fabstract%3Frss%3Dyes (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3070489 Wed, 09 Dec 2009 15:50:09 +0100 3070489 http://www.medworm.com/index.php?rid=3193071&cid=s_35571_60_f&fid=35571&url=http%3A%2F%2Fwww.febsletters.org%2Farticle%2FPIIS0014579309010436%2Fabstract%3Frss%3Dyes The NMR structure calculated for the PHD domain of ING4, which was found to have flexible N- and C-termini, has been revised. The revised structure has been deposited with the Protein Data Bank. The published supplementary , which contains the numerical statistics of the structure, should be replaced with a new table that corresponds to the actual deposited data in the PDB. The corrected supplementary table is given below. (Source: FEBS Letters) FEBS Letters journals http://www.medworm.com/rss/comments.php?id=3193071 Wed, 09 Dec 2009 00:00:00 +0100 3193071