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Protein chaperones

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https://www.readbyqxmd.com/read/28528489/the-ribosome-bound-quality-control-complex-from-aberrant-peptide-clearance-to-proteostasis-maintenance
#1
REVIEW
Quentin Defenouillère, Micheline Fromont-Racine
Proteostasis in eukaryotes is maintained by compartment-specific quality control pathways, which enable the refolding or the degradation of defective polypeptides to prevent the toxicity that may arise from their aggregation. Among these processes, translational protein quality control is performed by the Ribosome-bound Quality Control complex (RQC), which recognizes nascent peptides translated from aberrant mRNAs, polyubiquitylates these aberrant peptides, extracts them from the stalled 60S subunit and finally escorts them to the proteasome for degradation...
May 20, 2017: Current Genetics
https://www.readbyqxmd.com/read/28527593/a-structural-and-functional-study-of-gln147-deamidation-in-%C3%AE-a-crystallin-a-major-site-of-modification-in-human-cataract
#2
Nicholas J Ray, Damien Hall, John A Carver
Deamidation of Glu147 in human αA-crystallin is common in aged cataractous lenses (Hains and Truscott, Invest. Ophthalmol. Vis. Sci. 2010, 51, 3107). Accordingly, this modification may have a causative effect in cataract. αA-crystallin is a small heat-shock molecular chaperone protein that prevents aggregation of proteins and is the principal defence against crystallin protein unfolding and aggregation in the ageing lens. Deamidated Q147E αA-crystallin was structurally characterised using a variety of spectroscopic and biophysical methods, including NMR, circular dichroism and fluorescence spectroscopy and dynamic light scattering...
May 17, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28526855/gut-homeostasis-and-regulatory-t-cell-induction-depend-on-molecular-chaperone-gp96-in-cd11c-cells
#3
Yunpeng Hua, Yi Yang, Shaoli Sun, Stephen Iwanowycz, Caroline Westwater, Boris Reizis, Zihai Li, Bei Liu
The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. Intestinal professional antigen presenting cells (pAPCs) recognize and respond to the gut microbiota through multiple pattern-recognition receptors, including TLRs and NLRs. How gut pAPCs maintain mucosal homeostasis remains incompletely understood. Heat shock protein gp96, also known as grp94, is an essential immune chaperone for TLRs. However, the role of gp96 in regulating CD11c(+) APCs in the gut immunity and tolerance is unknown...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526614/human-aldehyde-dehydrogenase-3a1-aldh3a1-exhibits-chaperone-like-function
#4
Georgia-Persephoni Voulgaridou, Ilias Tsochantaridis, Theodora Mantso, Rodrigo Franco, Mihalis I Panayiotidis, Aglaia Pappa
Aldehyde dehydrogenase 3A1 (ALDH3A1) is a metabolic enzyme that catalyzes the oxidation of various aldehydes. Certain types of epithelial tissues in mammals, especially those continually exposed to environmental stress (e.g., corneal epithelium), express ALDH3A1 at high levels and its abundance in such tissues is perceived to help to maintain cellular homeostasis under conditions of oxidative stress. Metabolic as well as non-metabolic roles for ALDH3A1 have been associated with its mediated resistance to cellular oxidative stress...
May 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28526238/ric8a-is-essential-for-the-organisation-of-actin-cytoskeleton-and-cell-matrix-interaction
#5
Katrin Ruisu, Riho Meier, Keiu Kask, Tambet Tõnissoo, Teet Velling, Margus Pooga
RIC8A functions as a chaperone and guanine nucleotide exchange factor for a subset of G protein α subunits. Multiple G protein subunits mediate various signalling events that regulate cell adhesion and migration and the involvement of RIC8A in some of these processes has been demonstrated. We have previously shown that the deficiency of RIC8A causes a failure in mouse gastrulation and neurogenesis - major events in embryogenesis that rely on proper association of cells with the extracellular matrix (ECM) and involve active cell migration...
May 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28524086/dietary-green-pea-protects-against-dss-induced-colitis-in-mice-challenged-with-high-fat-diet
#6
Shima Bibi, Luís Fernando de Sousa Moraes, Noelle Lebow, Mei-Jun Zhu
Obesity is a risk factor for developing inflammatory bowel disease. Pea is unique with its high content of dietary fiber, polyphenolics, and glycoproteins, all of which are known to be health beneficial. We aimed to investigate the impact of green pea (GP) supplementation on the susceptibility of high-fat diet (HFD)-fed mice to dextran sulfate sodium (DSS)-induced colitis. Six-week-old C57BL/6J female mice were fed a 45% HFD or HFD supplemented with 10% GP. After 7-week dietary supplementation, colitis was induced by adding 2...
May 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28523271/the-protein-chaperone-clpx-targets-native-and-non-native-aggregated-substrates-for-remodeling-disassembly-and-degradation-with-clpp
#7
Christopher J LaBreck, Shannon May, Marissa G Viola, Joseph Conti, Jodi L Camberg
ClpX is a member of the Clp/Hsp100 family of ATP-dependent chaperones and partners with ClpP, a compartmentalized protease, to degrade protein substrates bearing specific recognition signals. ClpX targets specific proteins for degradation directly or with substrate-specific adaptor proteins. Native substrates of ClpXP include proteins that form large oligomeric assemblies, such as MuA, FtsZ, and Dps in Escherichia coli. To remodel large oligomeric substrates, ClpX utilizes multivalent targeting strategies and discriminates between assembled and unassembled substrate conformations...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#8
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#9
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28520954/h2b-ubiquitylation-and-the-histone-chaperone-asf1-cooperatively-mediate-the-formation-and-maintenance-of-heterochromatin-silencing
#10
Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen, Cheng-Fu Kao
Heterochromatin is a heritable form of gene repression, with critical roles in development and cell identity. Understanding how chromatin factors results in such repression is a fundamental question. Chromatin is assembled and disassembled during transcription, replication and repair by anti-silencing function 1 (Asf1), a highly conserved histone chaperone. Transcription and DNA replication are also affected by histone modifications that modify nucleosome dynamics, such as H2B ubiquitylation (H2Bub). We report here that H2Bub and Asf1 cooperatively promote transcriptional silencing at yeast telomeres and mating loci...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28520783/effect-of-n-terminal-region-of-nuclear-drosophila-melanogaster-small-heat-shock-protein-dmhsp27-on-function-and-quaternary-structure
#11
Mohamed Taha Moutaoufik, Geneviève Morrow, Stéphanie Finet, Robert M Tanguay
The importance of the N-terminal region (NTR) in the oligomerization and chaperone-like activity of the Drosophila melanogaster small nuclear heat shock protein DmHsp27 was investigated by mutagenesis using size exclusion chromatography and native gel electrophoresis. Mutation of two sites of phosphorylation in the N-terminal region, S58 and S75, did not affect the oligomerization equilibrium or the intracellular localization of DmHsp27 when transfected into mammalian cells. Deletion or mutation of specific residues within the NTR region delineated a motif (FGFG) important for the oligomeric structure and chaperone-like activity of this sHsp...
2017: PloS One
https://www.readbyqxmd.com/read/28520766/transcriptomic-analysis-of-salt-stress-responsive-genes-in-rhazya-stricta
#12
Nahid H Hajrah, Abdullah Y Obaid, Ahmed Atef, Ahmed M Ramadan, Dhivya Arasappan, Charllotte A Nelson, Sherif Edris, Mohammed Z Mutwakil, Alawia Alhebshi, Nour O Gadalla, Rania M Makki, Madgy A Al-Kordy, Fotouh M El-Domyati, Jamal S M Sabir, Mohammad A Khiyami, Neil Hall, Ahmed Bahieldin, Robert K Jansen
Rhazya stricta is an evergreen shrub that is widely distributed across Western and South Asia, and like many other members of the Apocynaceae produces monoterpene indole alkaloids that have anti-cancer properties. This species is adapted to very harsh desert conditions making it an excellent system for studying tolerance to high temperatures and salinity. RNA-Seq analysis was performed on R. stricta exposed to severe salt stress (500 mM NaCl) across four time intervals (0, 2, 12 and 24 h) to examine mechanisms of salt tolerance...
2017: PloS One
https://www.readbyqxmd.com/read/28516953/signal-recognition-particle-prevents-n-terminal-processing-of-bacterial-membrane-proteins
#13
Amitabh Ranjan, Evan Mercier, Arshiya Bhatt, Wolfgang Wintermeyer
Bacterial proteins are synthesized with an N-formylated amino-terminal methionine, and N-formylated peptides elicit innate-immunity responses against bacterial infections. However, the source of these formylated peptides is not clear, as most bacterial proteins are co-translationally deformylated by peptide deformylase. Here we develop a deformylation assay with translating ribosomes as substrates, to show that the binding of the signal recognition particle (SRP) to signal sequences in nascent proteins on the ribosome prevents deformylation, whereas deformylation of nascent proteins without signal sequence is not affected...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28515353/chaperone-mediated-autophagy-substrate-proteins-in-cancer
#14
REVIEW
Ying Tang, Xiong-Wen Wang, Zhan-Hua Liu, Yun-Ming Sun, Yu-Xin Tang, Dai-Han Zhou
All intracellular proteins undergo continuous synthesis and degradation. Chaperone-mediated autophagy (CMA) is necessary to maintain cellular homeostasis through turnover of cytosolic proteins (substrate proteins). This degradation involves a series of substrate proteins including both cancer promoters and suppressors. Since activating or inhibiting CMA pathway to treat cancer is still debated, targeting to the CMA substrate proteins provides a novel direction. We summarize the cancer-associated substrate proteins which are degraded by CMA...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515311/control-of-hsp90-chaperone-and-its-clients-by-n-terminal-acetylation-and-the-n-end-rule-pathway
#15
Jang-Hyun Oh, Ju-Yeon Hyun, Alexander Varshavsky
We found that the heat shock protein 90 (Hsp90) chaperone system of the yeast Saccharomyces cerevisiae is greatly impaired in naa10Δ cells, which lack the NatA N(α)-terminal acetylase (Nt-acetylase) and therefore cannot N-terminally acetylate a majority of normally N-terminally acetylated proteins, including Hsp90 and most of its cochaperones. Chk1, a mitotic checkpoint kinase and a client of Hsp90, was degraded relatively slowly in wild-type cells but was rapidly destroyed in naa10Δ cells by the Arg/N-end rule pathway, which recognized a C terminus-proximal degron of Chk1...
May 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28515276/assembly-of-the-u5-snrnp-component-prpf8-is-controlled-by-the-hsp90-r2tp-chaperones
#16
Anna Malinová, Zuzana Cvačková, Daniel Matějů, Zuzana Hořejší, Claire Abéza, Franck Vandermoere, Edouard Bertrand, David Staněk, Céline Verheggen
Splicing is catalyzed by the spliceosome, a complex of five major small nuclear ribonucleoprotein particles (snRNPs). The pre-mRNA splicing factor PRPF8 is a crucial component of the U5 snRNP, and together with EFTUD2 and SNRNP200, it forms a central module of the spliceosome. Using quantitative proteomics, we identified assembly intermediates containing PRPF8, EFTUD2, and SNRNP200 in association with the HSP90/R2TP complex, its ZNHIT2 cofactor, and additional proteins. HSP90 and R2TP bind unassembled U5 proteins in the cytoplasm, stabilize them, and promote the formation of the U5 snRNP...
May 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28510570/bag-1-as-a-biomarker-in-early-breast-cancer-prognosis-a-systematic-review-with-meta-analyses
#17
E S Papadakis, T Reeves, N H Robson, T Maishman, G Packham, R I Cutress
BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer...
May 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28510212/supercoiling-biases-the-formation-of-loops-involved-in-gene-regulation
#18
REVIEW
Laura Finzi, David Dunlap
The function of DNA as a repository of genetic information is well-known. The post-genomic effort is to understand how this information-containing filament is chaperoned to manage its compaction and topological states. Indeed, the activities of enzymes that transcribe, replicate, or repair DNA are regulated to a large degree by access. Proteins that act at a distance along the filament by binding at one site and contacting another site, perhaps as part of a bigger complex, create loops that constitute topological domains and influence regulation...
November 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28510050/a-review-of-multi-domain-and-flexible-molecular-chaperones-studies-by-small-angle-x-ray-scattering
#19
REVIEW
Júlio C Borges, Thiago V Seraphim, Paulo R Dores-Silva, Leandro R S Barbosa
Intrinsic flexibility is closely related to protein function, and a plethora of important regulatory proteins have been found to be flexible, multi-domain or even intrinsically disordered. On the one hand, understanding such systems depends on how these proteins behave in solution. On the other, small-angle X-ray scattering (SAXS) is a technique that fulfills the requirements to study protein structure and dynamics relatively quickly with few experimental limitations. Molecular chaperones from Hsp70 and Hsp90 families are multi-domain proteins containing flexible and/or disordered regions that play central roles in cellular proteostasis...
June 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28507559/the-dnaj-gene-family-in-pepper-capsicum-annuum-l-comprehensive-identification-characterization-and-expression-profiles
#20
FangFei Fan, Xian Yang, Yuan Cheng, Yunyan Kang, Xirong Chai
The DnaJ proteins which function as molecular chaperone played critical roles in plant growth and development and response to heat stress (HS) and also called heat shock protein 40 based on molecular weight. However, little was reported on this gene family in pepper. Recently, the release of the whole pepper genome provided an opportunity for identifying putative DnaJ homologous. In this study, a total of 76 putative pepper DnaJ genes (CaDnaJ01 to CaDnaJ76) were identified using bioinformatics methods and classified into five groups by the presence of the complete three domains (J-domain, zinc finger domain, and C-terminal domain)...
2017: Frontiers in Plant Science
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