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https://www.readbyqxmd.com/read/28095639/early-involvement-of-lysosome-dysfunction-in-the-degeneration-of-cerebral-cortical-neurons-caused-by-the-lipid-peroxidation-product-4-hydroxynonenal
#1
Shi Zhang, Erez Eitan, Mark P Mattson
Free radical-mediated oxidative damage to proteins, lipids and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy - lysosome pathway in rat primary cortical neurons...
January 17, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28059128/c-terminus-of-hsc70-interacting-protein-chip-inhibits-adipocyte-differentiation-via-ubiquitin-and-proteasome-mediated-degradation-of-ppar%C3%AE
#2
Jung-Hoon Kim, Soyeon Shin, Jinho Seo, Eun-Woo Lee, Manhyung Jeong, Min-Sik Lee, Hyun-Ji Han, Jaewhan Song
PPARγ (Peroxisome proliferator-activated receptor γ) is a nuclear receptor involved in lipid homeostasis and related metabolic diseases. Acting as a transcription factor, PPARγ is a master regulator for adipocyte differentiation. Here, we reveal that CHIP (C-terminus of HSC70-interacting protein) suppresses adipocyte differentiation by functioning as an E3 ligase of PPARγ. CHIP directly binds to and induces ubiquitylation of the PPARγ protein, leading to proteasome-dependent degradation. Stable overexpression or knockdown of CHIP inhibited or promoted adipogenesis, respectively, in 3T3-L1 cells...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28026090/the-mesenchymal-precursor-cell-marker-antibody-stro-1-binds-to-cell-surface-heat-shock-cognate-70
#3
Stephen Fitter, Stan Gronthos, Soo Siang Ooi, Andrew C W Zannettino
Since its discovery more than 25 years ago, the STRO-1 antibody has played a fundamental role in defining the hierarchical nature of mesenchymal precursor cells (MPC) and their progeny. STRO-1 antibody binding remains a hallmark of immature pluripotent MPC. Despite the significance of STRO-1 in the MPC field, the identity of the antigen has remained elusive. Using a combination of 2-dimensional gel electrophoresis, coupled with Western blotting and Tandem mass spectroscopy, we have identified the STRO-1 antigen as heat shock cognate 70 (HSC70;HSPA8)...
December 27, 2016: Stem Cells
https://www.readbyqxmd.com/read/27998983/bag1-promotes-trc8-dependent-degradation-of-misfolded-herg-potassium-channels
#4
Christine Hantouche, Brittany Williamson, William C Valinsky, Joshua Solomon, Alvin Shrier, Jason C Young
Cardiac long QT syndrome type 2 is caused by mutations in the hERG potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum, instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum, to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70 but this does not involve the Bag1 ubiquitin-like domain...
December 20, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27984043/myeloid-leukemia-factor-acts-in-a-chaperone-complex-to-regulate-transcription-factor-stability-and-gene-expression
#5
Jamie O Dyer, Arnob Dutta, Madelaine Gogol, Vikki M Weake, George Dialynas, Xilan Wu, Christopher Seidel, Ying Zhang, Laurence Florens, Michael P Washburn, Susan M Abmayr, Jerry L Workman
Mutations that affect Myeloid Leukemia Factor (MLF) proteins are associated with leukemia and several other cancers. However, with no strong homology to other proteins of known function, the role of MLF proteins in the cell has remained elusive. Here we describe a proteomics approach that identifies MLF as a member of a nuclear chaperone complex containing a DnaJ protein, BAG2 and Hsc70. This complex associates with chromatin and regulates expression of target genes. The MLF complex is bound to sites of nucleosome depletion and sites containing active chromatin marks (e...
October 27, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27966060/components-of-a-mammalian-protein-disaggregation-refolding-machine-are-targeted-to-nuclear-speckles-following-thermal-stress-in-differentiated-human-neuronal-cells
#6
Catherine A S Deane, Ian R Brown
Heat shock proteins (Hsps) are a set of highly conserved proteins involved in cellular repair and protective mechanisms. They counter protein misfolding and aggregation that are characteristic features of neurodegenerative diseases. Hsps act co-operatively in disaggregation/refolding machines that assemble at sites of protein misfolding and aggregation. Members of the DNAJ (Hsp40) family act as "holdases" that detect and bind misfolded proteins, while members of the HSPA (Hsp70) family act as "foldases" that refold proteins to biologically active states...
December 13, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27939888/chaperone-mediated-autophagy-promotes-lung-cancer-cell-survival-through-selective-stabilization-of-the-pro-survival-protein-mcl1
#7
Junya Suzuki, Wataru Nakajima, Hidenori Suzuki, Yumi Asano, Nobuyuki Tanaka
Autophagy is a dynamic recycling system using lysosomal proteolysis that produces new proteins and energy for cellular renovation and homeostasis. Although macroautophagy is known to serve as a survival pathway in many cancer cells, the role of chaperone-mediated autophagy (CMA), a selective protein degradation system, in cancer is not fully understood. Here, we demonstrated that lysosomal proteolysis, but not macroautophagy, attenuated apoptosis induced by the tyrosine kinase inhibitor, crizotinib, in the non-small-cell lung cancer (NSCLC) cell line, EBC1...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908666/molecular-cloning-and-expression-analysis-of-five-heat-shock-protein-70-hsp70-family-members-in-lateolabrax-maculatus-with-vibrio-harveyi-infection
#8
Ying-Li Han, Cong-Cong Hou, Chen Du, Jun-Quan Zhu
Heat shock proteins 70 (HSP70s) are molecular chaperones that aid in protection against environmental stress. In this study, we cloned and characterized five members of the HSP70 family (designated as HSPa1a, HSC70-1, HSC70-2, HSPa4 and HSPa14) from Lateolabrax maculatus using rapid amplification cDNA ends (RACE). Multiple sequence alignment and structural analysis revealed that all members of the HSP70 family had a conserved domain architecture, with some distinguishing features unique to each HSP70. Quantitative real-time (qPCR) analysis revealed that all members of the HSP70 family were ubiquitously and differentially expressed in all major types of tissues, including testicular tissue...
November 28, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27894884/modulation-of-the-heat-shock-response-is-associated-with-acclimation-to-novel-temperatures-but-not-adaptation-to-climatic-variation-in-the-ants-aphaenogaster-picea-and-a-rudis
#9
Sara Helms Cahan, Andrew D Nguyen, John Stanton-Geddes, Clint A Penick, Yainna Hernáiz-Hernández, Bernice B DeMarco, Nicholas J Gotelli
Ecological diversification into thermally divergent habitats can push species toward their physiological limits, requiring them to accommodate temperature extremes through plastic or evolutionary changes that increase persistence under the local thermal regime. One way to withstand thermal stress is to increase production of heat shock proteins, either by maintaining higher baseline abundance within cells or by increasing the magnitude of induction in response to heat stress. We evaluated whether environmental variation was associated with expression of three heat shock protein genes in two closely-related species of woodland ant, Aphaenogaster picea and A...
February 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27859498/the-srl-peptide-of-rhesus-rotavirus-vp4-protein-governs-cholangiocyte-infection-and-the-murine-model-of-biliary-atresia
#10
Sujit K Mohanty, Bryan Donnelly, Inna Lobeck, Ashley Walther, Phylicia Dupree, Abigail Coots, Jaroslaw Meller, Monica McNeal, Karol Sestak, Greg Tiao
: Biliary atresia (BA) is a neonatal obstructive cholangiopathy which progresses to end stage liver disease, often requiring transplantation. The murine model of BA, employing rhesus rotavirus (RRV), parallels human disease and has been used to elucidate mechanistic aspects of a virus induced biliary cholangiopathy. We previously reported that RRV VP4 gene plays an integral role in activating the immune system and induction of BA. Utilizing rotavirus binding and blocking assays, this study elucidated how RRV VP4 protein governs cholangiocyte susceptibility to infection both in vitro and in vivo in the murine model of BA...
November 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27852853/coat-protein-regulation-by-ck2-cpip-hsp70-and-chip-is-required-for-potato-virus-a-replication-and-coat-protein-accumulation
#11
Andres Lõhmus, Anders Hafrén, Kristiina Mäkinen
: We demonstrate here that coat protein (CP) phosphorylation by protein kinase CK2 and a chaperone system formed by two heat-shock proteins, CP-interacting protein (CPIP) and HSP70, are both essential for Potato virus A (PVA; genus Potyvirus) replication and that all of these host proteins have the capacity to contribute to the level of PVA CP accumulation. An E3 ubiquitin ligase called carboxyl terminus Hsc70-interacting protein (CHIP), which may participate in the CPIP-HSP70-mediated CP degradation, is also needed for robust PVA gene expression...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27835608/pc-1-works-in-conjunction-with-e3-ligase-chip-to-regulate-androgen-receptor-stability-and-activity
#12
Jian Wang, Hui Zhang, Xiaoqing Zhang, Peng Wang, Hongtao Wang, Fang Huang, Chenyan Zhou, Jianguang Zhou, Shanhu Li
The androgen receptor (AR) is not only a ligand-dependent transcription factor, but also functions as a licensing factor, a component of DNA replication, which is degraded during mitosis. Furthermore, the deregulation of AR activity is involved in the initiation of prostate cancer and contributes to castration resistant prostate cancer (CRPC). While AR degradation is known to occur primarily through a proteasome-mediated pathway, very little is known about how this process is regulated, especially in M phase...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833127/two-dimensional-gel-electrophoresis-based-proteomic-analysis-reveals-n-terminal-truncation-of-the-hsc70-protein-in-cotton-fibers-in-vivo
#13
Chengcheng Tao, Xiang Jin, Liping Zhu, Hongbin Li
On two-dimensional electrophoresis gels, six protein spots from cotton ovules and fibers were identified as heat shock cognate 70 kD protein (Hsc70). Three spots corresponded to an experimental molecular weight (MW) of 70 kD (spots 1, 2 and 3), and the remaining three spots corresponded to an experimental MW slightly greater than 45 kD (spots 4, 5 and 6). Protein spots 1, 2 and 3 were abundant on gels of 0-day (the day of anthesis) wild-type (WT) ovules, 0-day fuzzless-lintless mutant ovules and 10-day WT ovules but absent from gels of 10-day WT fibers...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807229/evidence-that-hsc70-is-associated-with-cucumber-necrosis-virus-particles-and-plays-a-role-in-particle-disassembly
#14
Syed Benazir Alam, D'Ann Rochon
: Uncoating of a virus particle to expose its nucleic acid is a critical aspect of the viral multiplication cycle, as it is essential for the establishment of infection. In the present study, we investigated the role of plant HSP70 homologs in the uncoating process of Cucumber necrosis virus (CNV), a nonenveloped positive-sense single-stranded RNA [(+)ssRNA] virus having a T=3 icosahedral capsid. We have found through Western blot analysis and mass spectrometry that the HSP70 homolog Hsc70-2 copurifies with CNV particles...
January 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27783273/hsp70-in-human-polymorphonuclear-and-mononuclear-leukocytes-comparison-of-the-protein-content-and-transcriptional-activity-of-hspa-genes
#15
Anna A Boyko, Tatyana L Azhikina, Maria A Streltsova, Alexander M Sapozhnikov, Elena I Kovalenko
Cell-type specific variations are typical for the expression of different members of the HSP70 family. In circulating immune cells, HSP70 proteins interact with units of signaling pathways involved in the immune responses and may promote cell survival in sites of inflammation. In this work, we compared basal HSP70 expression and stress-induced HSP70 response in polymorphonuclear and mononuclear human leukocytes. The intracellular content of inducible and constitutive forms of HSP70 was analyzed in relation to the transcriptional activity of HSPA genes...
October 25, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27757073/a-decade-of-boon-or-burden-what-has-the-chip-ever-done-for-cellular-protein-quality-control-mechanism-implicated-in-neurodegeneration-and-aging
#16
Vibhuti Joshi, Ayeman Amanullah, Arun Upadhyay, Ribhav Mishra, Amit Kumar, Amit Mishra
Cells regularly synthesize new proteins to replace old and abnormal proteins for normal cellular functions. Two significant protein quality control pathways inside the cellular milieu are ubiquitin proteasome system (UPS) and autophagy. Autophagy is known for bulk clearance of cytoplasmic aggregated proteins, whereas the specificity of protein degradation by UPS comes from E3 ubiquitin ligases. Few E3 ubiquitin ligases, like C-terminus of Hsc70-interacting protein (CHIP) not only take part in protein quality control pathways, but also plays a key regulatory role in other cellular processes like signaling, development, DNA damage repair, immunity and aging...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27709416/-1-h-15-n-and-13-c-resonance-assignments-for-free-and-ieevd-peptide-bound-forms-of-the-tetratricopeptide-repeat-domain-from-the-human-e3-ubiquitin-ligase-chip
#17
Huaqun Zhang, Cameron McGlone, Matthew M Mannion, Richard C Page
The ubiquitin ligase CHIP catalyzes covalent attachment of ubiquitin to unfolded proteins chaperoned by the heat shock proteins Hsp70/Hsc70 and Hsp90. CHIP interacts with Hsp70/Hsc70 and Hsp90 by binding of a C-terminal IEEVD motif found in Hsp70/Hsc70 and Hsp90 to the tetratricopeptide repeat (TPR) domain of CHIP. Although recruitment of heat shock proteins to CHIP via interaction with the CHIP-TPR domain is well established, alterations in structure and dynamics of CHIP upon binding are not well understood...
October 5, 2016: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/27706239/spatial-and-temporal-resolution-of-global-protein-synthesis-during-hsv-infection-using-bioorthogonal-precursors-and-click-chemistry
#18
Catherine Su Hui Teo, Remigiusz A Serwa, Peter O'Hare
We used pulse-labeling with the methionine analogue homopropargylglycine (HPG) to investigate spatiotemporal aspects of protein synthesis during herpes simplex virus (HSV) infection. In vivo incorporation of HPG enables subsequent selective coupling of fluorochrome-capture reagents to newly synthesised proteins. We demonstrate that HPG labeling had no effect on cell viability, on accumulation of test early or late viral proteins, or on overall virus yields. HPG pulse-labeling followed by SDS-PAGE analysis confirmed incorporation into newly synthesised proteins, while parallel processing by in situ cycloaddition revealed new insight into spatiotemporal aspects of protein localisation during infection...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27706135/the-epichaperome-is-an-integrated-chaperome-network-that-facilitates-tumour-survival
#19
Anna Rodina, Tai Wang, Pengrong Yan, Erica DaGama Gomes, Mark P S Dunphy, Nagavarakishore Pillarsetty, John Koren, John F Gerecitano, Tony Taldone, Hongliang Zong, Eloisi Caldas-Lopes, Mary Alpaugh, Adriana Corben, Matthew Riolo, Brad Beattie, Christina Pressl, Radu I Peter, Chao Xu, Robert Trondl, Hardik J Patel, Fumiko Shimizu, Alexander Bolaender, Chenghua Yang, Palak Panchal, Mohammad F Farooq, Sarah Kishinevsky, Shanu Modi, Oscar Lin, Feixia Chu, Sujata Patil, Hediye Erdjument-Bromage, Pat Zanzonico, Clifford Hudis, Lorenz Studer, Gail J Roboz, Ethel Cesarman, Leandro Cerchietti, Ross Levine, Ari Melnick, Steven M Larson, Jason S Lewis, Monica L Guzman, Gabriela Chiosis
Transient, multi-protein complexes are important facilitators of cellular functions. This includes the chaperome, an abundant protein family comprising chaperones, co-chaperones, adaptors, and folding enzymes-dynamic complexes of which regulate cellular homeostasis together with the protein degradation machinery. Numerous studies have addressed the role of chaperome members in isolation, yet little is known about their relationships regarding how they interact and function together in malignancy. As function is probably highly dependent on endogenous conditions found in native tumours, chaperomes have resisted investigation, mainly due to the limitations of methods needed to disrupt or engineer the cellular environment to facilitate analysis...
October 20, 2016: Nature
https://www.readbyqxmd.com/read/27702574/cell-free-analysis-of-polyq-dependent-protein-aggregation-and-its-inhibition-by-chaperone-proteins
#20
Kodai Machida, Tomoaki Shigeta, Ayano Kobayashi, Ai Masumoto, Yuna Hidaka, Hiroaki Imataka
Protein misfolding and aggregation is one of the major causes of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. So far protein aggregation related to these diseases has been studied using animals, cultured cells or purified proteins. In this study, we show that a newly synthesized polyglutamine protein implicated in Huntington's disease forms large aggregates in HeLa cells, and successfully recapitulate the process of this aggregation using a translation-based system derived from HeLa cell extracts...
December 10, 2016: Journal of Biotechnology
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