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Journal of Biological Chemistry

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https://www.readbyqxmd.com/read/27913625/absence-of-mir-146a-in-podocytes-increases-risk-of-diabetic-glomerulopathy-via-upregulation-of-erbb4-and-notch-1
#1
Ha Won Lee, Samia Q Khan, Shehryar Khaliqdina, Mehmet M Altintas, Florian Grahammer, Jimmy L Zhao, Kwihey Koh, Nicholas J Tardi, Mohd Hafeez Faridi, Terese Geraghty, David J Cimbaluk, Katalin Susztak, Luis F Moita, David Baltimore, Pierre-Louis Tharaux, Tobias B Huber, Matthias Kretzler, Markus Bitzer, Jochen Reiser, Vineet Gupta
Podocyte injury is an early event in diabetic kidney disease and is a hallmark of glomerulopathy. MicroRNA-146a (miR-146a) is highly expressed in many cell types under homeostatic conditions, and plays an important anti-inflammatory role in myeloid cells. However, its role in podocytes is unclear. Here, we show that miR-146a expression levels decrease in the glomeruli of patients with type 2 diabetes (T2D), which correlates with increased albuminuria and glomerular damage. MiR-146a levels are also significantly reduced in the glomeruli of albuminuric BTBR ob/ob mice, indicating its significant role in maintaining podocyte health...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913624/bcp1-is-the-nuclear-chaperone-of-the-60s-ribosomal-protein-rpl23-in-saccharomyces-cerevisiae
#2
Ya-Han Ting, Ting-Jun Lu, Arlen W Johnson, Jing-Ting Shie, Bo-Ru Chen, Suresh Kumar S, Kai-Yin Lo
Eukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913623/chac2-an-enzyme-for-slow-turnover-of-cytosolic-glutathione
#3
Amandeep Kaur, Ruchi Gautam, Ritika Srivastava, Avinash Chandel, Akhilesh Kumar, Subramanian Karthikeyan, Anand Kumar Bachhawat
Glutathione degradation plays an important role in glutathione and redox homeostasis and thus it is imperative to understand the enzymes and the mechanisms involved in glutathione degradation in detail. We describe here ChaC2, a member of the ChaC family of γ-glutamylcyclotransferases, as an enzyme that degrades glutathione in the cytosol of mammalian cells. ChaC2 is distinct from the previously described ChaC1, to which ChaC2 shows about 50% sequence identity. Human and mouse ChaC2 proteins, purified in vitro, show 10-20 fold lower catalytic efficiency than ChaC1, although they showed comparable Km values (Km of 3...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913622/a-venom-serpin-splicing-isoform-of-the-endoparasitoid-wasp-pteromalus-puparum-suppresses-host-prophenoloxidase-cascade-by-forming-complexes-with-host-hemolymph-proteinases
#4
Zhichao Yan, Qi Fang, Yang Liu, Shan Xiao, Lei Yang, Fei Wang, Chunju An, John H Werren, Gongyin Ye
To ensure successful parasitism, parasitoid wasps inject venom along with their eggs into their hosts. The venom serves to suppress host immune responses, including melanization. Venom from Pteromalus puparum, a pupal endoparasitoid, inhibits melanization of host hemolymph in vitro in a dose-dependent manner. Using assay guided fractionation, a serpin splicing isoform with phenoloxidase (PO) inhibitory activity was identified as P. puparum serpin-1, venom isoform (PpS1V). This serpin gene has 16 predicted splicing isoforms that differ only in the C-terminal region...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913621/identification-of-hepatic-lysophosphatidylcholine-acyltransferase-3-as-a-novel-target-gene-regulated-by-peroxisome-proliferator-activated-receptor-%C3%AE
#5
Amar Bahadur Singh, Jingwen Liu
Peroxisome proliferator-activated receptor δ (PPARδ) regulates many genes involved in lipid metabolism. Hepatic lysophosphatidylcholine acyltransferase 3 (LPCAT3) has critical functions in triglycerides transport and ER stress response due to its unique ability to catalyze the incorporation of polyunsaturated fatty acids into phospholipids. Previous studies identified liver X receptor as the transcription factor controlling LPCAT3 expression in mouse liver tissue. Here we show that the hepatic LPCAT3 gene is transcriptionally regulated by PPARδ...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913620/pb1-f2-derived-from-avian-influenza-a-virus-h7n9-induces-inflammation-via-activation-of-the-nlrp3-inflammasome
#6
Anita Pinar, Jennifer K Dowling, Natalie J Bitto, Avril B Robertson, Eicke Latz, Cameron R Stewart, Grant R Drummond, Matthew A Cooper, Julie L McAuley, Michelle D Tate, Ashley Mansell
The emergence of avian H7N9 influenza A virus (IAV) in humans with associated high mortality, has highlighted the threat of a potential pandemic. Fatal H7N9 infections are characterised by hyperinflammation and increased cellular infiltrates in the lung. Currently there are limited therapies to address the pathologies associated with H7N9 infection and what virulence factors may contribute to these pathologies. We have found that PB1-F2 derived from H7N9 activates the NLRP3 inflammasome and induces lung inflammation and cellular recruitment that is NLRP3 dependent...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909060/cd6-regulates-intestinal-ischemia-reperfusion-induced-injury-by-modulating-natural-igm-producing-b1a-cell-self-renewal
#7
Gospel Enyindah-Asonye, Yan Li, Wei Xin, Nora Singer, Neetu Gupta, John Fung, Feng Lin
Intestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease is poorly understood, although it is established that circulating pathogenic natural IgM, which is primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as a marker for T cells and later found to be present on some subsets of B cells in humans, however, whether CD6 plays any role in intestinal I/R induced injury and if so, what are the underlying mechanisms, remain unknown...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909059/the-role-of-the-histone-methyltransferase-enhancer-of-zeste-homolog-2-ezh2-in-the-pathobiological-mechanisms-underlying-inflammatory-bowel-disease-ibd
#8
Olga F Sarmento, Phyllis A Svingen, Yuning Xiong, Zhifu Sun, Adebowale O Bamidele, Angela J Mathison, Thomas C Smyrk, Asha A Nair, Michelle M Gonzalez, Mary R Sagstetter, Saurabh Baheti, Dermot P B McGovern, Jessica J Friton, Konstantinos A Papadakis, Goel Gautam, Ramnik J Xavier, Raul A Urrutia, William A Faubion
Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a pivotal role in maintaining immunologic self-tolerance. We and others have previously shown that EZH2 is recruited to the FOXP3 promoter and its targets in Treg cells. To further address the role for EZH2 in Treg cellular function, we have now generated mice that lack EZH2 specifically in Treg cells (EZH2ΔFOXP3+). We find that EZH2 deficiency in FOXP3+ T cells results in lethal multi-organ autoimmunity. We further demonstrate that EZH2ΔFOXP3+ T cells lack a regulatory phenotype in vitro and secrete pro-inflammatory cytokines...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909058/secreted-glioblastoma-nanovesicles-contain-intracellular-signaling-proteins-and-active-ras-incorporated-in-a-farnesylation-dependent-manner
#9
Natalie Luhtala, Aaron Aslanian, John R Yates, Tony Hunter
Glioblastomas (GBMs) are malignant brain tumors with a median survival of less than 18 months. Redundancy of signaling pathways represented within GBMs contributes to their therapeutic resistance. Exosomes are extracellular nanovesicles released from cells and present in human biofluids that represent a possible biomarker of tumor signaling state that could aid in personalized treatment. Herein, we demonstrate that mouse GBM cell-derived extracellular nanovesicles resembling exosomes from an H-RasV12 myr-Akt mouse model for GBM are enriched for intracellular signaling cascade proteins (GO: 0007242) and Ras protein signal transduction (GO: 0007265), and contain active Ras...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909057/structure-of-the-tir-domain-of-bcap-which-links-phosphoinositide-metabolism-with-the-negative-regulation-of-the-tlr-signalosome
#10
Samer Halabi, Eiki Sekine, Brett Verstack, Nicholas J Gay, Martin C Moncrieffe
Ligand binding to Toll-like receptors (TLRs) results in dimerization of their cytosolic TIR domains and recruitment of post-receptor signal transducers into a complex signalosome. TLR activation leads to the production of transcription factors, pro-inflammatory molecules and the activation of Phosphoinositide 3-kinases (PI3K) in a process that requires the multi-modular B-cell Adaptor for Phosphoinositide 3-kinase (BCAP). BCAP has a sequence previously proposed as a "cryptic" TIR domain. Here, we present the structure of the N-terminal region of human BCAP and show that it possesses a canonical TIR-fold...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909056/interferons-induce-expression-of-samhd1-in-monocytes-through-downregulation-of-mir-181a-and-mir-30a
#11
Maximilan Riess, Nina V Fuchs, Adam Idica, Matthias Hamdorf, Egbert Flory, Irene Munk Pedersen, Renate König
SAMHD1 is a phosphohydrolase maintaining cellular dNTP homeostasis but also acts as a critical regulator in innate immune responses due to its antiviral activity and association with autoimmune disease leading to aberrant activation of interferon. SAMHD1 expression is differentially regulated by interferon in certain primary cells, but the underlying mechanism is not understood. Here, we report a detailed characterization of the promotor region, the 5' and 3' untranslated region (UTR) of SAMHD1, and the mechanism responsible for the cell-type dependent upregulation of SAMHD1 protein by interferon...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909055/molecular-identification-of-d-ribulokinase-in-budding-yeast-and-mammals
#12
Charandeep Singh, Enrico Glaab, Carole L Linster
Proteomes of even well characterized organisms still contain a high percentage of proteins with unknown or uncertain molecular and/or biological function. A significant fraction of those proteins are predicted to have catalytic properties. Here we aimed at identifying the function of the Saccharomyces cerevisiae Ydr109c protein and of its human homolog FGGY, both of which belong to the broadly conserved FGGY family of carbohydrate kinases. Functionally identified members of this family phosphorylate 3- to 7-carbon sugars or sugar derivatives, but the endogenous substrate of S...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909054/identification-of-a-substrate-selective-exosite-within-the-metalloproteinase-anthrax-lethal-factor
#13
Allison B Goldberg, Eunice Cho, Chad J Miller, Hua Jane Lou, Benjamin E Turk
The metalloproteinase anthrax lethal factor (LF) is secreted by Bacillus anthracis to promote disease virulence through disruption of host signaling pathways. LF is a highly specific protease, exclusively cleaving mitogen-activated protein kinase kinases (MKKs) and rodent NACHT leucine-rich repeat and pyrin domain containing protein 1B (NLRP1B). How LF achieves such restricted substrate specificity is not understood. Previous studies have suggested the existence of an exosite interaction between LF and MKKs that promotes cleavage efficiency and specificity...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909053/endoplasmic-reticulum-stress-and-ca2-depletion-differentially-modulate-the-sterol-regulatory-protein-pcsk9-to-control-lipid-metabolism
#14
Paul Lebeau, Ali Al-Hashimi, Sudesh Sood, Sarka Lhotak, Pei Yu, Gabriel Gyulay, Guillaume Pare, S R Wayne Chen, Bernardo Trigatti, Annik Prat, Nabil Seidah, Richard C Austin
Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER localized transcription factor that directly upregulates sterol-regulatory genes, including PCSK9. Given that PCSK9 contributes to atherosclerosis by targeting low-density lipoprotein (LDL) receptor (LDLR) degradation, our present study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909050/notch-pathway-is-activated-via-genetic-and-epigenetic-alterations-and-is-a-therapeutic-target-in-clear-cell-renal-cancer
#15
Tushar D Bhagat, Yiyu Zou, Shizeng Huang, Jihwan Park, Matthew B Palmer, Caroline Hu, Wejuan Li, Niraj Shenoy, Orsolya Giricz, Gaurav Choudhary, Yiting Yu, Yi-An Ko, Maria C Izquierdo, Ae Seo Deok Park, Nishanth Vallumsetla, Remi Laurence, Robert Lopez, Masako Suzuki, James Pullman, Justin Kaner, Benjamin Gartrell, A Ari Hakimi, John M Greally, Bharvin Patel, Karim Benhadji, Kith Pradhan, Amit Verma, Katalin Susztak
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq dataset also revealed widespread activation of NOTCH pathway in a large cohort of CCRCC samples. Samples with NOTCH pathway activation were also clinically distinct and were associated with better overall survival...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909049/control-of-secreted-protein-gene-expression-and-the-mammalian-secretome-by-the-metabolic-regulator-pgc-1%C3%AE
#16
Neri Minsky, Robert G Roeder
Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. However, how the secretome is regulated remains incompletely understood. Here we demonstrate, unexpectedly, that peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909048/the-ph-dependence-of-saccharides-influence-on-thermal-denaturation-of-two-model-proteins-supports-an-excluded-volume-model-for-stabilization-generalized-to-allow-for-intramolecular-electrostatic-interactions
#17
Ilyas Beg, Allen P Minton, Asimul Islam, Md Imtaiyaz Hassan, Faizan Ahmad
The reversible thermal denaturation of apo alpha-lactalbumin and lysozyme was measured in the absence and presence of multiple concentrations of each of seven saccharides (glucose, galactose, fructose, sucrose, trehalose, raffinose and stachyose) at multiple pH values. It was observed that with increasing pH, the absolute stability of alpha-lactalbumin decreased while the stabilizing effect per mole of all saccharides increased, and that the absolute stability of lysozyme increased, while the stabilizing effect per mole of all saccharides decreased...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909052/spontaneous-unfolding-refolding-of-fibronectin-type-iii-domains-assayed-by-thiol-exchange-thermodynamic-stability-correlates-with-rates-of-unfolding-rather-than-folding
#18
Riddhi Shah, Tomoo Ohashi, Harold P Erickson, Terrence G Oas
Globular proteins are not permanently folded, but spontaneously unfold and refold on time scales that can span orders of magnitudes for different proteins. A long-standing debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study we have determined the unfolding and folding kinetics of ten FNIII domains. FNIII domains are one of the most common protein folds, and are present in 2% of animal proteins. FNIII domains are ideal for this study because they have an identical 7-strand beta sandwich structure, but they vary widely in sequence and thermodynamic stability...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909051/the-chaperone-activity-and-substrate-spectrum-of-human-small-heat-shock-proteins
#19
Evgeny V Mymrikov, Marina Daake, Bettina Richter, Martin Haslbeck, Johannes Buchner
Small heat shock proteins (sHsps) are a ubiquitous family of molecular chaperones that suppress the unspecific aggregation of miscellaneous proteins. Multicellular organisms contain a large number of different sHsps, raising questions as to whether they function redundantly or are specialized in terms of substrates and mechanism. To gain insight into this issue, we undertook a comparative analysis of the 8 major human sHsps on the aggregation of both model proteins and cytosolic lysates under standardized conditions...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903654/carbon-and-acyl-chain-flux-during-stress-induced-triglyceride-accumulation-by-stable-isotopic-labeling-of-the-polar-microalga-coccomyxa-subellipsoidea-c169
#20
James W Allen, Concetta C DiRusso, Paul N Black
Deriving biofuels and other lipoid products from algae is a promising future technology directly addressing global issues of atmospheric CO2 balance. To better understand the metabolism of triglyceride synthesis in algae, we examined their metabolic origins in the model species, Coccomyxa subellipsoidea C169, using stable isotopic labeling. Labeling patterns arising from (13)C-U-glucose, (13)CO2, or D2O supplementation were analyzed by GC-MS and/or LC-MS over time courses during nitrogen (N) starvation to address the roles of catabolic carbon (C) recycling, acyl chain redistribution, and de novo fatty acid (FA) synthesis during the expansion of the lipid bodies...
November 30, 2016: Journal of Biological Chemistry
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