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https://www.readbyqxmd.com/read/28096332/human-nf-%C3%AE%C2%BAb-repressing-factor-acts-as-a-stress-regulated-switch-for-ribosomal-rna-processing-and-nucleolar-homeostasis-surveillance
#1
Marta Coccia, Antonio Rossi, Anna Riccio, Edoardo Trotta, Maria Gabriella Santoro
The nucleolus, a dynamic nuclear compartment long regarded as the cell ribosome factory, is emerging as an important player in the regulation of cell survival and recovery from stress. In larger eukaryotes, the stress-induced transcriptional response is mediated by a family of heat-shock transcription factors. Among these, HSF1, considered the master regulator of stress-induced transcriptional responses, controls the expression of cytoprotective heat shock proteins (HSPs), molecular chaperones/cochaperones constituting a major component of the cell protein quality control machinery essential to circumvent stress-induced degradation and aggregation of misfolded proteins...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28091697/heat-shock-transcription-factor-1-protects-against-pressure-overload-induced-cardiac-fibrosis-via-smad3
#2
Ning Zhou, Yong Ye, Xingxu Wang, Ben Ma, Jian Wu, Lei Li, Lin Wang, Dao Wen Wang, Yunzeng Zou
: Fibrotic cardiac muscle exhibits high stiffness and low compliance which are major risk factors of heart failure. Although heat shock transcription factor 1 (HSF1) was identified as an intrinsic cardioprotective factor, the role that HSF1 plays in cardiac fibrosis remains unclear. Our study aims to investigate the role of HSF1 in pressure overload-induced cardiac fibrosis and the underlying mechanism. HSF1 phosphorylation was significantly downregulated in transverse aortic constriction (TAC)-treated mouse hearts and mechanically stretched cardiac fibroblasts (cFBs)...
January 13, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28089856/erythrocyte-heat-shock-protein-responses-to-chronic-in-vivo-and-acute-in-vitro-temperature-challenge-in-diploid-and-triploid-salmonids
#3
Pillai V Saranyan, Neil W Ross, Tillmann J Benfey
This research investigated how ploidy level (diploid versus triploid) affects the heat shock protein (HSP) response in erythrocytes under different thermal stress regimes, both in vivo and in vitro, in Atlantic salmon (Salmo salar) and brook charr (Salvelinus fontinalis) in order to address the question of why triploids typically have reduced thermal tolerance. A preliminary study confirmed that identical volumes of diploid and triploid erythrocytes (which equates to a smaller number of larger cells for triploids compared to diploids) did not differ in total protein synthesis rates...
January 13, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28052564/regulation-of-the-mammalian-heat-shock-factor-1
#4
REVIEW
Sharadha Dayalan Naidu, Albena T Dinkova-Kostova
Living organisms are endowed with the capability to tackle various forms of cellular stress due to the presence of molecular chaperone machinery complexes that are ubiquitous throughout the cell. During conditions of proteotoxic stress, the transcription factor heat shock factor 1 (HSF1) mediates the elevation of heat shock proteins, which are crucial components of the chaperone complex machinery and function to ameliorate protein misfolding and aggregation and restore protein homeostasis. In addition, HSF1 orchestrates a versatile transcriptional program that includes genes involved in repair and clearance of damaged macromolecules and maintenance of cell structure and metabolism, and provides protection against a broad range of cellular stress mediators, beyond heat shock...
January 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28049024/1-4-naphthoquinone-activates-the-hsp90-hsf1-pathway-through-the-s-arylation-of-hsp90-in-a431-cells-negative-regulation-of-the-redox-signal-transduction-pathway-by-persulfides-polysulfides
#5
Yumi Abiko, Liang Sha, Yasuhiro Shinkai, Takamitsu Unoki, Nho Cong Luong, Yukihiro Tsuchiya, Yasuo Watanabe, Reiko Hirose, Takaaki Akaike, Yoshito Kumagai
The current consensus is that environmental electrophiles activate redox signal transduction pathways through covalent modification of sensor proteins with reactive thiol groups at low concentrations, while they cause cell damage at higher concentrations. We previously exposed human carcinoma A431 cells to the atmospheric electrophile 1,4-naphthoquinone (1,4-NQ) and found that heat shock protein 90 (HSP90), a negative regulator of heat shock factor 1 (HSF1), was a target of 1,4-NQ. In the study presented here, we determined whether 1,4-NQ activates HSF1...
December 31, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28031489/unrestrained-ampylation-targets-cytosolic-chaperones-and-activates-the-heat-shock-response
#6
Matthias C Truttmann, Xu Zheng, Leo Hanke, Jadyn R Damon, Monique Grootveld, Joanna Krakowiak, David Pincus, Hidde L Ploegh
Protein AMPylation is a conserved posttranslational modification with emerging roles in endoplasmic reticulum homeostasis. However, the range of substrates and cell biological consequences of AMPylation remain poorly defined. We expressed human and Caenorhabditis elegans AMPylation enzymes-huntingtin yeast-interacting protein E (HYPE) and filamentation-induced by cyclic AMP (FIC)-1, respectively-in Saccharomyces cerevisiae, a eukaryote that lacks endogenous protein AMPylation. Expression of HYPE and FIC-1 in yeast induced a strong cytoplasmic Hsf1-mediated heat shock response, accompanied by attenuation of protein translation, massive protein aggregation, growth arrest, and lethality...
December 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28009259/principles-of-systems-biology-no-12
#7
(no author information available yet)
This month: Plants take center stage with fascinating insights into disease susceptibility and engineered pathways for photosynthesis. Also, a wearable stethoscope, new noncanonical miRNA targeting rules, Hsf1, and transcription.
December 21, 2016: Cell Systems
https://www.readbyqxmd.com/read/28004573/discovery-of-a-chemical-probe-bisamide-cct251236-an-orally-bioavailable-efficacious-pirin-ligand-from-a-heat-shock-transcription-factor-1-hsf1-phenotypic-screen
#8
Matthew D Cheeseman, Nicola E A Chessum, Carl S Rye, A Elisa Pasqua, Michael J Tucker, Birgit Wilding, Lindsay E Evans, Susan Lepri, Meirion Richards, Swee Y Sharp, Salyha Ali, Martin Rowlands, Lisa O'Fee, Asadh Miah, Angela Hayes, Alan T Henley, Marissa Powers, Robert Te Poele, Emmanuel De Billy, Loredana Pellegrino, Florence Raynaud, Rosemary Burke, Rob L M van Montfort, Suzanne A Eccles, Paul Workman, Keith Jones
Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27997575/the-heat-shock-transcription-factor-hsf1-induces-ovarian-cancer-epithelial-mesenchymal-transition-in-a-3d-spheroid-growth-model
#9
Chase D Powell, Trillitye R Paullin, Candice Aoisa, Christopher J Menzie, Ashley Ubaldini, Sandy D Westerheide
Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. The proteotoxic stress-responsive transcription factor HSF1 is frequently overexpressed in a variety of cancers and is vital to cellular proliferation and invasion in some cancers. Upon analysis of various patient data sets, we find that HSF1 is frequently overexpressed in ovarian tumor samples. In order to determine the role of HSF1 in ovarian cancer, inducible HSF1 knockdown cell lines were created...
2016: PloS One
https://www.readbyqxmd.com/read/27979920/molecular-mechanisms-that-distinguish-tfiid-housekeeping-from-regulatable-saga-promoters
#10
Wim J de Jonge, Eoghan O'Duibhir, Philip Lijnzaad, Dik van Leenen, Marian Ja Groot Koerkamp, Patrick Kemmeren, Frank Cp Holstege
An important distinction is frequently made between constitutively expressed housekeeping genes versus regulated genes. Although generally characterized by different DNA elements, chromatin architecture and cofactors, it is not known to what degree promoter classes strictly follow regulatability rules and which molecular mechanisms dictate such differences. We show that SAGA-dominated/TATA-box promoters are more responsive to changes in the amount of activator, even compared to TFIID/TATA-like promoters that depend on the same activator Hsf1...
December 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27975203/loss-of-malin-but-not-laforin-results-in-compromised-autophagic-flux-and-proteasomal-dysfunction-in-cells-exposed-to-heat-shock
#11
Navodita Jain, Anupama Rai, Rohit Mishra, Subramaniam Ganesh
Heat stress to a cell leads to the activation of heat shock response, which is required for the management of misfolded and unfolded proteins. Macroautophagy and proteasome-mediated degradation are the two cellular processes that degrade polyubiquitinated, misfolded proteins. Contrasting pieces of evidence exist on the effect of heat stress on the activation of the above-mentioned degradative pathways. Laforin phosphatase and malin E3 ubiquitin ligase, the two proteins defective in Lafora neurodegenerative disorder, are involved in cellular stress response pathways and are required for the activation of heat shock transcription factor - the heat shock factor 1 (HSF1) - and, consequently, for cellular protection under heat shock...
December 14, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27966061/ubl-bag-domain-co-chaperones-cause-cellular-stress-upon-overexpression-through-constitutive-activation-of-hsf1
#12
Esben G Poulsen, Caroline Kampmeyer, Franziska Kriegenburg, Jens V Johansen, Kay Hofmann, Christian Holmberg, Rasmus Hartmann-Petersen
As a result of exposure to stress conditions, mutations, or defects during synthesis, cellular proteins are prone to misfold. To cope with such partially denatured proteins, cells mount a regulated transcriptional response involving the Hsf1 transcription factor, which drives the synthesis of molecular chaperones and other stress-relieving proteins. Here, we show that the fission yeast Schizosaccharomyces pombe orthologues of human BAG-1, Bag101, and Bag102, are Hsp70 co-chaperones that associate with 26S proteasomes...
December 14, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27951587/mrna-quality-control-is-bypassed-for-immediate-export-of-stress-responsive-transcripts
#13
Gesa Zander, Alexandra Hackmann, Lysann Bender, Daniel Becker, Thomas Lingner, Gabriela Salinas, Heike Krebber
Cells grow well only in a narrow range of physiological conditions. Surviving extreme conditions requires the instantaneous expression of chaperones that help to overcome stressful situations. To ensure the preferential synthesis of these heat-shock proteins, cells inhibit transcription, pre-mRNA processing and nuclear export of non-heat-shock transcripts, while stress-specific mRNAs are exclusively exported and translated. How cells manage the selective retention of regular transcripts and the simultaneous rapid export of heat-shock mRNAs is largely unknown...
December 12, 2016: Nature
https://www.readbyqxmd.com/read/27934604/generation-of-induced-pluripotent-stem-cells-ipscs-stably-expressing-crispr-based-synergistic-activation-mediator-sam
#14
Kai Xiong, Yan Zhou, Poul Hyttel, Lars Bolund, Kristine Karla Freude, Yonglun Luo
Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4 and C-MYC. We have validated that the reprogramming cassette is silenced in the SAM iPSC clones. Expression of pluripotency genes (OCT4, SOX2, LIN28A, NANOG, GDF3, SSEA4, and TRA-1-60), differentiation potential to all three germ layers, and normal karyotypes are validated...
November 17, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27926536/a-minimal-titration-model-of-the-mammalian-dynamical-heat-shock-response
#15
Aude Sivéry, Emmanuel Courtade, Quentin Thommen
Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene regulatory network of the HSR that reproduces quantitatively different heat shock experiments both on heat shock factor 1 (HSF1) and HSPs activities...
December 7, 2016: Physical Biology
https://www.readbyqxmd.com/read/27924568/visualization-of-ras-mapk-signaling-in-situ-by-the-proximity-ligation-assay-pla
#16
Zijian Tang, Chengkai Dai
RAS/MAPK signaling responds to diverse extracellular cues and regulates a wide array of cellular processes. Given its biological importance, abnormalities in RAS/MAPK signaling cascade have been intimately implicated in numerous human diseases, including cancer. Herein, we describe a novel methodology to study activation of this pivotal signaling pathway. The Proximity Ligation Assay (PLA) is employed to monitor kinase-substrate interactions between MEK1 and HSF1, or MEK1 and ERK1 in situ.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27922674/2-hydroxycinnamaldehyde-induces-apoptosis-through-hsf1-mediated-bag3-expression
#17
Hai-Anh Nguyen, Soo-A Kim
BAG3, a member of BAG co-chaperone family, is induced by stressful stimuli such as heat shock and heavy metals. Through interaction with various binding partners, BAG3 is thought to play a role in cellular adaptive responses against stressful conditions in normal and neoplastic cells. 2'-Hydroxycinnamaldehyde (HCA) is a natural derivative of cinnamaldehyde and has antitumor activity in various cancer cells. In the present study, for the first time, we identified that HCA induced BAG3 expression and BAG3-mediated apoptosis in cancer cells...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27909049/control-of-secreted-protein-gene-expression-and-the-mammalian-secretome-by-the-metabolic-regulator-pgc-1%C3%AE
#18
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 γ coactivator 1-α (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate the expression of diverse genes encoding secreted molecules and extracellular matrix components to modulate the secretome...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27906968/structural-and-functional-recovery-of-sensory-cilia-in-c-elegans-ift-mutants-upon-aging
#19
Astrid Cornils, Ashish K Maurya, Lauren Tereshko, Julie Kennedy, Andrea G Brear, Veena Prahlad, Oliver E Blacque, Piali Sengupta
The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27890044/effect-of-dietary-manganese-on-antioxidant-status-and-expressions-of-heat-shock-proteins-and-factors-in-tissues-of-laying-broiler-breeders-under-normal-and-high-environmental-temperatures
#20
Yong-Wen Zhu, Lin Lu, Wen-Xiang Li, Li-Yang Zhang, Cheng Ji, Xi Lin, Hsiao-Ching Liu, Jack Odle, Xu-Gang Luo
To investigate the effect of Mn on antioxidant status and on the expressions of heat shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21±1°C, and high, 32±1°C)×3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in any of the measured indices...
December 2016: British Journal of Nutrition
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