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FEBS Letters

Boren Lin, Da Xu, Douglas W Leaman
X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a cytokine-regulated, tumor necrosis factor (TNF) receptor-associated factor (TRAF) domain-containing protein that has a poorly defined cellular function. Here, we show that ectopically-expressed XAF1 inhibits TNF-ɑ-induced NF-κB activation, whereas shRNA silencing of endogenous XAF1 augments it. Our data suggest that XAF1 may inhibit TNF-ɑ-induced NF-κB activation by disrupting assembly of the TRADD/TRAF2/RIP1 complex (complex I) downstream of TNF receptor activation...
October 21, 2016: FEBS Letters
Przemyslaw Jurczak, Patrick Groves, Aneta Szymanska, Sylwia Rodziewicz-Motowidlo
Human cystatin C (hCC) is a small protein belonging to the cystatin family of papain-like cysteine proteinase inhibitors. We review the recent literature concerning structural aspects of hCC related to disease. We focus on the mechanisms of hCC dimerization, oligomerization and amyloid formation. Amyloid formation is associated with a number of neurodegenerative diseases that affect the independence and quality of life of aging populations. hCC is one of the second wave proteins that have been found to undergo amyloidosis associated with disease...
October 19, 2016: FEBS Letters
Ryan J Mailloux, Adrian Young, Julia Chalker, Danielle Gardiner, Marisa O'Brien, Liam Slade, John T Brosnan
Here, we report that choline and dimethylglycine can stimulate reactive oxygen species (ROS) production in liver mitochondria. Choline stimulated O2(●-) /H2 O2 at a concentration of 5 μM. We also observed that Complex II and III inhibitors, atpenin A5 and myxothiazol, collectively induced a 95% decrease in O2(●-) /H2 O2 production indicating both sites serve as the main sources of ROS during choline oxidation. Dimethylglycine, an intermediate of choline oxidation, was a more effective ROS generator. Rates of production were ~43% higher than choline-mediated O2(●-) /H2 O2 production...
October 19, 2016: FEBS Letters
Renata Voltolini Velho, Raffaella De Pace, Henning Tidow, Thomas Braulke, Sandra Pohl
The disease-associated hexameric N-acetylglucosamine (GlcNAc)-1-phosphotransferase complex (α2 β2 γ2 ) catalyzes the formation of mannose 6-phosphate residues on lysosomal enzymes required for efficient targeting to lysosomes. Using pull-down experiments and mutant subunits, we identified a potential loop-like region in the α-subunits comprising residues 535-588 and 645-698 involved in the binding to γ-subunits. The interaction is independent of the mannose 6-phosphate receptor homology domain but requires the N-terminal unstructured part of the γ-subunit consisting of residues 26-69...
October 13, 2016: FEBS Letters
Xiyao Liu, Huiqing Wang, Zhiyun Zhu, Yongyi Ye, Hengxu Mao, Shizhong Zhang
Growing evidence indicates that microRNAs (miRNAs) play vital roles in glioma progression by directly regulating multiple targets. Here, we found that miR-105 expression was significantly decreased and inversely correlated with SOX9 mRNA expression in glioma tissues. SOX9 was identified as a direct target of miR-105. miR-105 up-regulation repressed the expression of SOX9, TCF4, c-MYC, cyclin D1, and AXIN2 and suppressed glioma cell progression. Restoration of SOX9 or TCF4 abolished the effect of miR-105 on glioma cell progression...
October 13, 2016: FEBS Letters
Anne Lorenz, Vinay Pawar, Susanne Häussler, Siegfried Weiss
Pseudomonas aeruginosa is an important opportunistic pathogen that can cause acute respiratory infections in immunocompetent patients or chronic infections in immunocompromised individuals and in patients with cystic fibrosis. When acquiring the chronic infection state, bacteria are encapsulated within biofilm structures enabling them to withstand diverse environmental assaults, including immune reactions and antimicrobial therapy. Understanding the molecular interactions within the bacteria, as well as with the host or other bacteria, is essential for developing innovative treatment strategies...
October 12, 2016: FEBS Letters
L Patrick Schenck, Michael G Surette, Dawn M E Bowdish
The intestinal microbiota is essential for nutrient acquisition, immune development, and exclusion of invading pathogens. The upper respiratory tract (URT) microbiota is less well studied and does not appear to abide by many of the paradigms of the gastrointestinal tract. Decades of carriage studies in children have demonstrated that microbe-microbe competition and collusion occurs in the URT. Whether colonization with common pathogens (e.g. Staphylococcus aureus and Streptococcus pneumoniae) alters immune development or susceptibility to respiratory conditions is just beginning to be understood...
October 12, 2016: FEBS Letters
Hyang-Mi Lee, Ji-Sun Kim, Sa-Ouk Kang
Despite the importance of glutathione in Dictyostelium, the role of glutathione synthetase (gshB/GSS) has not been clearly investigated. In this study, we observed that increasing glutathione content by constitutive expression of gshB leads to mound-arrest and defects in cAMP-mediated aggregation and developmental gene expression. The overexpression of gpaB encoding G protein alpha 2 (Gα2), an essential component of the cAMP signaling pathway, results in a phenotype similar to that caused by gshB overexpression, whereas gpaB knockdown in gshB-overexpressing cells partially rescues the abovementioned phenotypic defects...
October 8, 2016: FEBS Letters
Sylvie Callegari, Frank Richter, Katarzyna Chojnacka, Daniel C Jans, Isotta Lorenzi, David Pacheu-Grau, Stefan Jakobs, Christof Lenz, Henning Urlaub, Jan Dudek, Agnieszka Chacinska, Peter Rehling
Hydrophobic inner mitochondrial membrane proteins with internal targeting signals, such as the metabolite carriers, use the carrier translocase (TIM22 complex) for transport into the inner membrane. Defects in this transport pathway have been associated with neurodegenerative disorders. While the TIM22 complex is well studied in baker's yeast, very little is known about the mammalian TIM22 complex. Using immunoprecipitation, we purified the human carrier translocase and identified a mitochondrial inner membrane protein TIM29 as a novel component, specific to metazoa...
October 8, 2016: FEBS Letters
Seo-Ree Choi, Yeo-Jin Seo, Minjae Kim, Yumi Eo, Hee-Chul Ahn, Ae-Ree Lee, Chin-Ju Park, Kyoung-Seok Ryu, Hae-Kap Cheong, Shim Sung Lee, Eon Seon Jin, Joon-Hwa Lee
The quaternary-amino-ethyl 1 (QAE1) isoforms of type III antifreeze proteins (AFPs) prevent the growth of ice crystals within organisms living in polar regions. We determined the antifreeze activity of wild-type and mutant constructs of the Japanese notched-fin eelpout (Zoarces elongates Kner) AFP8 (nfeAFP8), and characterized the structural and dynamics properties of their ice-binding surface using NMR. We found that the three constructs containing the V20G mutation were incapable of stopping the growth of ice crystals and exhibited structural changes, as well as increased conformational flexibility, in the first 310 helix (residues 18 - 22) of the sequence...
October 8, 2016: FEBS Letters
Mitsuhiro Hisadome, Tomokazu Ohnishi, Kyoko Kakimoto, Joji Kusuyama, Kenjiro Bandow, Takuro Kanekura, Tetsuya Matsuguchi
Keratinocytes secrete vascular endothelial growth factor (VEGF) and angioregulatory chemokines during cutaneous wound healing. Hepatocyte growth factor (HGF) promotes skin re-epithelialization by increasing VEGF expression in keratinocytes. Here, we investigated the regulatory roles of HGF in the expression of genes encoding angiogenic and angiostatic chemokines in keratinocytes and found that HGF specifically inhibits mRNA expression of the angiostatic chemokine CXCL10 in both mouse primary keratinocytes and in the human keratinocyte cell line HaCaT through the MEK/ERK cascade...
October 8, 2016: FEBS Letters
Masayoshi Higashiguchi, Izumi Nagatomo, Takashi Kijima, Osamu Morimura, Kotaro Miyake, Toshiyuki Minami, Shohei Koyama, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
We identified CHK2 K373E as a recurrent mutation in The Cancer Genome Atlas (TCGA) database. In this study, we demonstrate that the K373E mutation disrupts CHK2 autophosphorylation as well as kinase activity, thus leading to impairment of CHK2 functions in suppressing cell proliferation and promoting cell survival after ionizing radiation. We propose that K373E impairs p53-independent induction of p21(WAF)(1/)(CIP)(1) by CHK2. Our data implicate the K373E mutation of CHK2 in tumorigenesis. This article is protected by copyright...
October 7, 2016: FEBS Letters
Liyan Wang, Xiaotong Bo, Qinghua Zheng, Xuhua Xiao, Linling Wu, Bin Li
MiR-296 was previously reported to be underexpressed in hepatocellular carcinoma (HCC). However, the clinical value of miR-296 and its function in HCC remain poorly understood. In this study, we found that miR-296 levels are decreased in HCC specimens and cells, and that the underexpression of miR-296 is associated with adverse clinical parameters and poor overall survival rate. In vitro experiments indicate that miR-296 inhibits proliferation, colony formation, and cell-cycle progression and enhances apoptosis in HCC cells...
October 7, 2016: FEBS Letters
Delphine Kapps, Marta Cela, Anne Théobald-Dietrich, Tamara Hendrickson, Magali Frugier
In this Review, we examine the so-called 'OB-fold', a tRNA-binding domain homologous to the bacterial tRNA-binding protein Trbp111. We highlight the ability of OB-fold homologs to bind tRNAs and summarize their distribution in evolution. Nature has capitalized on the advantageous effects acquired when an OB-fold domain binds to tRNA by evolutionarily selecting this domain for fusion to different enzymes. Here, we review our current understanding of how the complexity of OB-fold containing proteins and enzymes developed to expand their functions, especially in unicellular, pathogenic eukaryotes...
October 7, 2016: FEBS Letters
Giel H Scheepers, Jelger A Lycklama A Nijeholt, Bert Poolman
Substrate-binding proteins (SBPs) play an important role in solute uptake and signal transduction. In 2010 Berntsson et al. classified the 114 organism-specific SBP structures available at that time and defined six protein clusters, based on their structural similarity. Since then the number of unique SBP structures has increased almost 5-fold, whereas the number of protein entries in the Protein Data Bank (PDB) nearly doubled. On the basis of the much larger dataset, we now sub-classify the SBPs within the original clusters...
October 7, 2016: FEBS Letters
Jia Jia Lim, Youngjin Lee, So Young Yoon, Tue Tu Ly, Jung Youn Kang, Hyung-Seop Youn, Jun Yop An, Jung-Gyu Lee, Kyoung Ryoung Park, Tae Gyun Kim, Jin Kuk Yang, Youngsoo Jun, Soo Hyun Eom
The interaction of the rhomboid pseudoprotease Derlin-1 and p97 is crucial for the retrotranslocation of polyubiquitinated substrates in the endoplasmic reticulum-associated degradation (ERAD) pathway. We report a 2.25 Å resolution structure of the p97 N-terminal domain (p97N) in complex with the Derlin-1 SHP motif. Remarkably, the SHP motif adopts a short, antiparallel β-strand that interacts with the β-sheet of p97N-a site distinct from that to which most p97 adaptor proteins bind. Mutational and biochemical analyses contributed to defining the specific interaction, demonstrating the importance of a highly conserved binding pocket on p97N and a signature motif on SHP...
October 7, 2016: FEBS Letters
Henrietta W Bennett, Na Liu, Yan Hu, Megan C King
We have developed a high-throughput sequencing approach that enables us to determine terminal telomere sequences from tens of thousands of individual Schizosaccharomyces pombe telomeres. This method provides unprecedented coverage of telomeric sequence complexity in fission yeast. S. pombe telomeres are composed of modular degenerate repeats that can be explained by variation in usage of the TER1 RNA template during reverse transcription. Taking advantage of this deep sequencing approach, we find that "like" repeat modules are highly correlated within individual telomeres...
October 7, 2016: FEBS Letters
Natalia Gruba, Jose Ignacio Rodriguez Martinez, Renata Grzywa, Magdalena Wysocka, Marcin Skoreński, Michał Burmistrz, Maria Łęcka, Adam Lesner, Marcin Sieńczyk, Krzysztof Pyrć
Zika virus (ZIKV), isolated from macaques in Uganda in 1947, was not considered to be a dangerous human pathogen. However, this view has recently changed as ZIKV infections are now associated with serious pathological disorders including microcephaly and Guillain-Barré syndrome. Similar to other viruses in the Flaviviridae family, ZIKV expresses the serine protease NS3 which is responsible for viral protein processing and replication. Herein, we report the expression of an active NS3(pro) domain fused with the NS2B cofactor (NS2BLN NS3(pro) ) in a prokaryotic expression system and profile its specificity for synthesized FRET-type substrate libraries...
October 7, 2016: FEBS Letters
Li Chen, David R Brigstock
Exosomes mediate intercellular microRNA delivery between hepatic stellate cells (HSC), the principal fibrosis-producing cells in the liver. The purpose of this study was to identify receptors on HSC for HSC-derived exosomes, which bind to HSC rather than to hepatocytes. Our findings indicate that exosome binding to HSC is blocked by treating HSC with RGD, EDTA, integrin αv or β1 siRNAs, integrin αvβ3 or α5β1 neutralizing antibodies, heparin, or sodium chlorate. Furthermore, exosome cargo delivery and exosome-regulated functions in HSC, including expression of fibrosis- or activation-associated genes and/or miR-214 target gene regulation, are dependent on cellular integrin αvβ3, integrin α5β1, or heparan-sulfate proteolgycans (HSPG)...
October 7, 2016: FEBS Letters
Shekhar Saha, Debdatta Halder, Swagata Goswami, Siddhartha S Jana
In this study, we investigated the regions in the alternatively spliced C2 insert of non-muscle myosin (NM) II-C conferring unique functional properties to the protein. We used constructs carrying deletions within different regions of C2 in neuronal cells; namely, the polar N-terminal, the proline/serine-rich middle, and the nonpolar C-terminal. We compared the wild-type NM II-C2 and deletion mutants with respect to ATPase activity, co-assembly with NM II-B, regulation by myosin light-chain kinase (MLCK), and solubility, to determine the C2 region(s) involved in these processes...
October 7, 2016: FEBS Letters
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