scholarly journals PARP1 promotes the human heat shock response by facilitating HSF1 binding to DNA

2018 ◽  
pp. MCB.00051-18 ◽  
Author(s):  
Mitsuaki Fujimoto ◽  
Ryosuke Takii ◽  
Arpit Katiyar ◽  
Pratibha Srivastava ◽  
Akira Nakai
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Mammalian Cells ◽  
Ternary Complex ◽  
Regulatory Mechanisms ◽  
Gene Body ◽  
Shock Response ◽  
Shock Proteins ◽  
Transcription Factor 1

The heat shock response (HSR) is characterized by the rapid and robust induction of heat shock proteins (HSPs), including HSP70, in response to heat shock, and is regulated by heat shock transcription factor 1 (HSF1) in mammalian cells. Poly(ADP-ribose) polymerase 1 (PARP1), which can form a complex with HSF1 through the scaffold protein PARP13, has been suggested to be involved in the HSR. However, its effects on and regulatory mechanisms of the HSR are not well understood. Here, we show that prior to heat shock the HSF1-PARP13-PARP1 complex binds to HSP70 promoter. In response to heat shock, activated and auto-PARylated PARP1 dissociates from HSF1-PARP13 and redistributes throughout HSP70 locus. Remarkably, chromatin in HSP70 promoter is initially PARylated at high levels and decondensed, whereas that in the gene body is moderately PARylated afterwards. Activated HSF1 then binds to the promoter efficiently, and promotes the HSR. Chromatin PARylation and HSF1 binding to the promoter are also facilitated by phosphorylation-dependent dissociation of PARP13. Furthermore, the HSR and proteostasis capacity are reduced by pretreatment with genotoxic stresses, which disrupt the ternary complex. These results provide one of the priming mechanisms of the HSR that facilitates HSF1 binding to DNA during heat shock.

scholarly journals The Role of Heat Shock Transcription Factor 1 in the Genome-wide Regulation of the Mammalian Heat Shock Response

2004 ◽  
Vol 15 (3) ◽  
pp. 1254-1261 ◽  
Author(s):  
Nathan D. Trinklein ◽  
John I. Murray ◽  
Sara J. Hartman ◽  
David Botstein ◽  
Richard M. Myers
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Mammalian Cells ◽  
Transcriptional Response ◽  
Heat Shock Transcription Factor ◽  
Genome Wide ◽  
Shock Response ◽  
Inducible Genes ◽  
Transcription Factor 1

Previous work has implicated heat shock transcription factor 1 (HSF1) as the primary transcription factor responsible for the transcriptional response to heat stress in mammalian cells. We characterized the heat shock response of mammalian cells by measuring changes in transcript levels and assaying binding of HSF1 to promoter regions for candidate heat shock genes chosen by a combination of genome-wide computational and experimental methods. We found that many heat-inducible genes have HSF1 binding sites (heat shock elements, HSEs) in their promoters that are bound by HSF1. Surprisingly, for 24 heat-inducible genes, we detected no HSEs and no HSF1 binding. Furthermore, of 182 promoters with likely HSE sequences, we detected HSF1 binding at only 94 of these promoters. Also unexpectedly, we found 48 genes with HSEs in their promoters that are bound by HSF1 but that nevertheless did not show induction after heat shock in the cell types we examined. We also studied the transcriptional response to heat shock in fibroblasts from mice lacking the HSF1 gene. We found 36 genes in these cells that are induced by heat as well as they are in wild-type cells. These results provide evidence that HSF1 does not regulate the induction of every transcript that accumulates after heat shock, and our results suggest that an independent posttranscriptional mechanism regulates the accumulation of a significant number of transcripts.

scholarly journals Disruption of the three cytoskeletal networks in mammalian cells does not affect transcription, translation, or protein translocation changes induced by heat shock.

1985 ◽  
Vol 5 (7) ◽  
pp. 1571-1581 ◽  
Author(s):  
W J Welch ◽  
J R Feramisco
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Mammalian Cells ◽  
Stress Proteins ◽  
Protein Translocation ◽  
Shock Response ◽  
Cytochalasin E ◽  
Cytoskeletal Networks ◽  
Shock Proteins ◽  
Cytoskeletal Elements

Mammalian cells show a complex series of transcriptional and translational switching events in response to heat shock treatment which ultimately lead to the production and accumulation of a small number of proteins, the so-called heat shock (or stress) proteins. We investigated the heat shock response in both qualitative and quantitative ways in cells that were pretreated with drugs that specifically disrupt one or more of the three major cytoskeletal networks. (These drugs alone, cytochalasin E and colcemid, do not result in induction of the heat shock response.) Our results indicated that disruption of the actin microfilaments, the vimentin-containing intermediate filaments, or the microtubules in living cells does not hinder the ability of the cell to undergo an apparently normal heat shock response. Even when all three networks were simultaneously disrupted (resulting in a loose, baglike appearance of the cells), the cells still underwent a complete heat shock response as assayed by the appearance of the heat shock proteins. In addition, the major induced 72-kilodalton heat shock protein was efficiently translocated from the cytoplasm into its proper location in the nucleus and nucleolus irrespective of the condition of the three cytoskeletal elements.

Disruption of the three cytoskeletal networks in mammalian cells does not affect transcription, translation, or protein translocation changes induced by heat shock

1985 ◽  
Vol 5 (7) ◽  
pp. 1571-1581
Author(s):  
W J Welch ◽  
J R Feramisco
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Mammalian Cells ◽  
Stress Proteins ◽  
Protein Translocation ◽  
Shock Response ◽  
Cytochalasin E ◽  
Cytoskeletal Networks ◽  
Shock Proteins ◽  
Cytoskeletal Elements

Mammalian cells show a complex series of transcriptional and translational switching events in response to heat shock treatment which ultimately lead to the production and accumulation of a small number of proteins, the so-called heat shock (or stress) proteins. We investigated the heat shock response in both qualitative and quantitative ways in cells that were pretreated with drugs that specifically disrupt one or more of the three major cytoskeletal networks. (These drugs alone, cytochalasin E and colcemid, do not result in induction of the heat shock response.) Our results indicated that disruption of the actin microfilaments, the vimentin-containing intermediate filaments, or the microtubules in living cells does not hinder the ability of the cell to undergo an apparently normal heat shock response. Even when all three networks were simultaneously disrupted (resulting in a loose, baglike appearance of the cells), the cells still underwent a complete heat shock response as assayed by the appearance of the heat shock proteins. In addition, the major induced 72-kilodalton heat shock protein was efficiently translocated from the cytoplasm into its proper location in the nucleus and nucleolus irrespective of the condition of the three cytoskeletal elements.

Urea sensitizes mIMCD3 cells to heat shock-induced apoptosis: protection by NaCl

2001 ◽  
Vol 280 (3) ◽  
pp. C614-C620 ◽  
Author(s):  
Chantal Colmont ◽  
Stéphanie Michelet ◽  
Dominique Guivarc'h ◽  
Germain Rousselet
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Heat Sensitivity ◽  
Osmotic Gradient ◽  
Water Reabsorption ◽  
Apoptotic Pathway ◽  
Shock Response ◽  
Induced Apoptosis ◽  
Shock Proteins ◽  
Dose Dependent

Urea, with NaCl, constitutes the osmotic gradient that allows water reabsorption in mammalian kidneys. Because NaCl induces heat shock proteins, we tested the responses to heat shock of mIMCD3 cells adapted to permissive urea and/or NaCl concentrations. We found that heat-induced cell death was stronger after adaptation to 250 mM urea. This effect was reversible, dose dependent, and, interestingly, blunted by 125 mM NaCl. Moreover, we have shown that urea-adapted cells engaged in an apoptotic pathway upon heat shock, as shown by DNA laddering. This sensitization is not linked to a defect in the heat shock response, because the induction of HSP70 was similar in isotonic and urea-adapted cells. Moreover, it is not linked to the presence of urea inside cells, because washing urea away did not restore heat resistance and because applying urea and heat shock at the same time did not lead to heat sensitivity. Together, these results suggest that urea modifies the heat shock response, leading to facilitated apoptosis.

scholarly journals Changes in Membrane Fluid State and Heat Shock Response Cause Attenuation of Virulence

2010 ◽  
Vol 192 (7) ◽  
pp. 1999-2005 ◽  
Author(s):  
Amalia Porta ◽  
Annamaria Eletto ◽  
Zsolt Török ◽  
Silvia Franceschelli ◽  
Attila Glatz ◽  
...  
Keyword(s):  
Heat Shock ◽  
Genetic Modification ◽  
Heat Shock Response ◽  
Mammalian Cells ◽  
Histoplasma Capsulatum ◽  
Genetic Manipulation ◽  
Microbial Pathogens ◽  
Fluid State ◽  
Shock Response ◽  
Serovar Typhimurium

ABSTRACT So far attenuation of pathogens has been mainly obtained by chemical or heat treatment of microbial pathogens. Recently, live attenuated strains have been produced by genetic modification. We have previously demonstrated that in several prokaryotes as well as in yeasts and mammalian cells the heat shock response is controlled by the membrane physical state (MPS). We have also shown that in Salmonella enterica serovar Typhimurium LT2 (Salmonella Typhimurium) overexpression of a Δ12-desaturase gene alters the MPS, inducing a sharp impairment of transcription of major heat shock genes and failure of the pathogen to grow inside macrophage (MΦ) (A. Porta et al., J. Bacteriol. 192:1988-1998, 2010). Here, we show that overexpression of a homologous Δ9-desaturase sequence in the highly virulent G217B strain of the human fungal pathogen Histoplasma capsulatum causes loss of its ability to survive and persist within murine MΦ along with the impairment of the heat shock response. When the attenuated strain of H. capsulatum was injected in a mouse model of infection, it did not cause disease. Further, treated mice were protected when challenged with the virulent fungal parental strain. Attenuation of virulence in MΦ of two evolutionarily distant pathogens was obtained by genetic modification of the MPS, suggesting that this is a new method that may be used to produce attenuation or loss of virulence in both other intracellular prokaryotic and eukaryotic pathogens. This new procedure to generate attenuated forms of pathogens may be used eventually to produce a novel class of vaccines based on the genetic manipulation of a pathogen's membrane fluid state and stress response.

scholarly journals The long noncoding RNA NEAT1 and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response

2018 ◽  
Vol 293 (49) ◽  
pp. 18965-18976 ◽  
Author(s):  
S. Mohammad Lellahi ◽  
Ingrid Arctander Rosenlund ◽  
Annica Hedberg ◽  
Liv Torill Kiær ◽  
Ingvild Mikkola ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Shock Response

scholarly journals Se Alleviated Oxidative Stress-Mediated Complex Poisoning Mechanism in Pb-Treated Chicken Kidneys: Inflammation, Heat Shock Response, and Autophagy

2021 ◽  
Author(s):  
Zhiying Miao ◽  
Weikang Yu ◽  
Yueyang Wang ◽  
Xianhong Gu ◽  
Xiaohua Teng
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Protein Expression ◽  
Heat Shock Response ◽  
Potable Water ◽  
Histological Structure ◽  
Standard Diet ◽  
Shock Response ◽  
Mrna And Protein Expression ◽  
Shock Proteins

Abstract Background: Lead (Pb) is a toxic environmental pollutant and can exerts toxicity in kidneys. It is known that selenium (Se) has an antagonistic effect on Pb poisoning. However, biological events during the process were not well understood in chicken kidneys.Methods: One hundred and eighty male Hyline chickens (7-day-old) were randomly divided into the control group (offering standard diet and potable water), the Se group (offering Na2SeO3-added standard diet and potable water), the Pb group (offering standard diet and (CH3OO)2Pb-added potable water), and the Pb+Se group (offering Na2SeO3-added standard diet and (CH3OO)2Pb-added potable water). On 30th, 60th, and 90th days, kidneys were removed to perform the studies of histological structure, oxidative stress indicators, cytokines, heat shock proteins, and autophagy in the chicken kidneys.Results: The experimental results indicated that Pb poisoning changed renal histological structure; decreased catalase, glutathione-s-transferase, and total antioxidative capacity activities; increased hydrogen peroxide content; induced mRNA and protein expression of heat shock proteins; inhibited interleukin (IL)-2 mRNA expression, and induced IL-4 and IL-12β mRNA expression; inhibited mammalian target of rapamycin mRNA and protein expression, and induced autophagy-related gene mRNA and protein expression in the chicken kidneys. Supplement of Se mitigated the above changes caused by Pb.Conclusion: Our research strengthens the evidence that Pb induced oxidative stress, inflammation, heat shock response, and autophagy and Se administration alleviated Pb poisoning through mitigating oxidative stress in the chicken kidneys.

scholarly journals Regulatory effect of heat shock transcription factor-1 gene on heat shock proteins and its transcriptional regulation analysis in small abalone Haliotis diversicolor

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Zhang ◽  
Yuting Li ◽  
Yulong Sun ◽  
Mingxing Guo ◽  
Jianjun Feng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Binding Site ◽  
Promoter Activity ◽  
Luciferase Activity ◽  
Haliotis Diversicolor ◽  
Shock Response ◽  
Flanking Region ◽  
Small Abalone ◽  
Shock Proteins

Abstract Background The effects of diverse stresses ultimately alter the structures and functions of proteins. As molecular chaperones, heat shock proteins (HSPs) are a group of highly conserved proteins that help in the refolding of misfolded proteins and the elimination of irreversibly damaged proteins. They are mediated by a family of transcription factors called heat shock factors (HSFs). The small abalone Haliotis diversicolor is a species naturally distributed along the southern coast of China. In this study, the expression of HdHSF1 was inhibited by RNAi in hemocytes in order to further elucidate the regulatory roles of HdHSF1 on heat shock responsive genes in abalone. Meanwhile, to understand the transcriptional regulation of the HdHSF1 gene, the 5′-upstream regulatory region of HdHSF1 was characterized, and the relative promoter activity was examined by dual-luciferase reporter gene assay system in HEK293T cell lines. Results After the inhibition of the H. diversicolor HSF1 gene (HdHSF1) by dsRNA (double-stranded RNA), the expression of most heat shock related-genes was down-regulated (p < 0.05). It indicated the importance of HdHSF1 in the heat shock response of H. diversicolor. Meanwhile, 5′-flanking region sequence (2633 bp) of the HdHSF1 gene was cloned; it contained a putative core promoter region, TATA box, CAAT box, CpG island, and many transcription elements. In HEK293T cells, the 5′-flanking region sequence can drive expression of the enhanced green fluorescent protein (EGFP), proving its promoter function. Exposure of cells to the high-temperature (39 °C and 42 °C) resulted in the activation of HdHSF1 promoter activity, which may explain why the expression of the HdHSF1 gene participates in heat shock response. Luciferase activity of different recombinant plasmids, which contained different truncated promoter fragments of the HdHSF1 gene in HEK293T cells, revealed the possible active regions of the promoter. To further identify the binding site of the critical transcription factor in the region, an expression vector with the site-directed mutation was constructed. After being mutated on the GATA-1 binding site, we found that the luciferase activity was significantly increased, which suggested that the GATA-1 binding site has a certain weakening effect on the activity of the HdHSF1 promoter. Conclusions These findings suggest that GATA-1 may be one of the transcription factors of HdHSF1, and a possible signaling pathway mediated by HdHSF1 may exist in H. diversicolor to counteract the adverse effects of heat shock stress.

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