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Heat Shock Transcription Factors: Structure and Regulation
Abstract
Organisms respond to elevated temperatures and to chemical and physiological stresses by an increase in the synthesis of heat shock proteins. The regulation of heat shock gene expression in eukaryotes is mediated by the conserved heat shock transcription factor (HSF). HSF is present in a latent state under normal conditions; it is activated upon heat stress by induction of trimerization and high-affinity binding to DNA and by exposure of domains for transcriptional activity. Analysis of HSF cDNA clones from many species has defined structural and regulatory regions responsible for the inducible activities. The heat stress signal is thought to be transduced to HSF by changes in the physical environment, in the activity of HSF-modifying enzymes. or by changes in the intracellular level of heat shock proteins.
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“HSP90 transcription is controlled by the heat shock transcription factor HSF, a key regulator of the heat shock response36,37 that is evolutionarily conserved from S. cerevisiae (Hsf1) to mammals (HSF1/2).”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [37]
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“In eukaryotes, heat-shock-dependent gene transcription requires the binding of the transcription factor HSF to specific sequences in the heatshock genes (Morimoto 1998; Trott and Morano 2003; Schöffl et al. 1998; Wu 1995).”
Park, K.-W., Hahn, J., Fan, Q., Thiele, D. J., & Li, L. (2006) · Genetics · doi:10.1534/genetics.105.054221 · Cited by 32
“HSFs are structurally and functionally conserved from yeast to humans, containing a winged helix-turn-helix DNA-binding domain, a hydrophobic stretch necessary for homotrimerization, followed by a transcription activation domain that is also conserved (Wu 1995; Littlefield and Nelson 2001).”
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Temperature responsiveness of gilthead sea bream bone; an in vitro and in vivo approach
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“This activation is mediated in part by heat shock transcription factors (HSF), whose fundamental architecture and heat shock element (HSE) binding site are conserved from yeast to humans (Wu, 1995; Littlefield and Nelson, 1999; Akerfelt et al., 2007).”
BackgroundFujimoto, M., Takii, R., Katiyar, A., Srivastava, P., & Nakai, A. (2018) · Molecular and Cellular Biology · doi:10.1128/mcb.00051-18 · Cited by 29
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“The HSR is mainly regulated at the level of transcription by evolutionarily conserved heat shock transcription factors (HSFs) that bind to HSR elements (HSEs) in eukaryotes (Wu, 1995; Morimoto, 1998; Nakai, 2016; Gomez-Pastor et al , 2018).”
Blocking HSF1 by Dominant-Negative Mutant to Sensitize Tumor Cells to Hyperthermia
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BackgroundHSP70 and Constitutively Active HSF1 Mediate Protection Against CDCrel-1-mediated Toxicity
Jung, A. E., Fitzsimons, H. L., Bland, R. J., During, M. J., & Young, D. (2008) · Molecular Therapy · doi:10.1038/mt.2008.68 · Cited by 28
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“…& 2006 Nature Publishing Group All rights reserved 0950-9232/06 $30.00 www.nature.com/onc Transcription of many HSPs is induced via the transcriptional activator, heat shock factor 1 (Hsf1; Morimoto et al., 1992, 1998; Wu, 1995; Pirkkala et al., 2001; Ravagnan et al., 2001; Voellmy, 2004).”
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BackgroundTo Sense or Die: Mechanisms of Temperature Sensing in Fungal Pathogens
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BackgroundHeat shock transcription factors regulate heat induced cell death in a rat histiocytoma
Prasad, K. V., Taiyab, A., Jyothi, D., et al. (2007) · Journal of Biosciences · doi:10.1007/s12038-007-0058-4 · Cited by 28
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“HSF1 is activated in roughly two steps (1, 8, 9).”
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“The deletion of the HR-C domain results in constitutive trimerization which may explain why HSF4, that lacks this domain, has a constitutive DNA-binding ability [19].”
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“…1 3 0 EVOLUTION MAY 2015 with HSF-1, a transcription factor known to regulate a number of heat shock proteins to mediate heat stress response (Wu 1995; Åkerfelt et al. 2010; Baird et al. 2014), and SKN-1, whose regulatory targets are important for resistance to both oxidative and starvation…”
BackgroundCell surface and relative mRNA expression of heat shock protein 70 in human synovial cells
Sedláčková, L., Nguyen, T. T. H., Zlacká, D., et al. (2008) · Autoimmunity · doi:10.1080/08916930802227466 · Cited by 27
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“The HSF family includes hsf1, the molecular coordinator of the heat shock response, as well as two less characterized heat shock factors hsf2 and hsf4 [15-19] .”
BackgroundCoactivator ASC‐2 mediates heat shock factor 1‐mediated transactivation dependent on heat shock
Hong, S., Kim, S. H., Heo, M. A., et al. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00028-6 · Cited by 27
Heat Shock Proteins in Renal Cell Carcinomas
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The effect of heat stress and cadmium ions on the expression of a small hsp gene in barley and maize
Gullì, M., Rampino, P., Lupotto, E., et al. (2005) · Journal of Cereal Science · doi:10.1016/j.jcs.2005.01.006 · Cited by 27
Analysis of heat shock transcription factor for suppression of polyglutamine toxicity
Rimoldi, M., Servadio, A., & Zimarino, V. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00602-5 · Cited by 27
Suppression of heat shock transcription factor HSF1 in zebrafish causes heat‐induced apoptosis
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“In lower organisms such as yeast and Drosophila, control of the heat shock response is accomplished by a single Hsf gene (Wu, 1995).”
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HSF-1: Guardian of the Proteome Through Integration of Longevity Signals to the Proteostatic Network
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“The N-terminal region of approximately the first 100 amino acids is the most well-conserved region of the HSF protein family and encodes a helix-turn-helix loop DNA-binding domain (DBD), which recognizes DNA heat shock elements (HSE) (identified as nGAAn DNA repeats) (Wu 1995).”
BackgroundSong, J., Zhao, H., Zhang, L., Li, Z., Han, J., Zhou, C., Xu, J., Li, X., & Yan, X. (2023) · Plant and Cell Physiology · doi:10.1093/pcp/pcad023 · Cited by 26
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“Hsf1, the master transcriptional regulator of the heat shock response genes 53 , constitutively associates with heat shock elements (HSEs) at the promoter 54–57 under both non-heat shock (NHS) and heat shock (HS) conditions (Fig.”
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“The regulation of HSP activity occurs mainly at the transcriptional level, via highly conserved HSEs located in the promoters of the HSP genes (Schöffl et al. 1998; Wu 1995).”
BackgroundHSF1-Mediated Regulation of Tumor Cell Apoptosis: A Novel Target for Cancer Therapeutics
Kumar, S., Tomar, M. S., & Acharya, A. (2013) · Future Oncology · doi:10.2217/fon.13.106 · Cited by 26
Regulation of Translation Factor EEF1D Gene Function by Alternative Splicing
Kaitsuka, T., & Matsushita, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16023970 · Cited by 27
“In response to various inducers, such as heat shock, most HSFs acquire DNA binding activity and bind to HSEs, thereby inducing the transcription of genes encoding Hsps [39,45–47].”
BackgroundPolyamines mediate glutamine-dependent induction of the intestinal epithelial heat shock response
Iwashita, Y., Sakiyama, T., Musch, M. W., Ropeleski, M. J., Tsubouchi, H., & Chang, E. B. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00054.2011 · Cited by 26
“Glutamine is needed as a substrate for the synthesis of polyamines, which in turn facilitates HSF-1 binding to HSE.”
BackgroundInfluentialHSF1 and HSF3 cooperatively regulate the heat shock response in lizards
Takii, R., Fujimoto, M., Matsuura, Y., Wu, F., Oshibe, N., Takaki, E., Katiyar, A., Akashi, H. D., Makino, T. T., Kawata, M., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180776 · Cited by 25
Resolution, Detection, and Characterization of Redox Conformers of Human HSF1
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“The immediate initiation of transcription of heatinducible hsp-genes is mainly due to activation of one (or two) heat shock factor(s) (HSF; Wu, 1995).”
BackgroundHeat Shock Proteins in Human Perilymph: Implications for Cochlear Implantation
Schmitt, H., Roemer, A., Zeilinger, C., Salcher, R. B., Ďurišin, M., Staecker, H., Lenarz, T., & Warnecke, A. (2017) · Otology & Neurotology · doi:10.1097/mao.0000000000001625 · Cited by 25
“Unaut also controlling different stress responsive nuclear activities and interferes with heat shock factor 1 (23,24).”
BackgroundGao, X., Wang, Q., Feng, Q., Zhang, B., He, C., Luo, H., & An, B. (2022) · Journal of Fungi · doi:10.3390/jof8020175 · Cited by 25
“The HSE consists of three contiguous repeats of the short sequence 5′-nGAAn-3′ [61].”
BackgroundTaylor, D., Tradewell, M. L., Minotti, S., & Durham, H. D. (2005) · Cell Stress and Chaperones · doi:10.1379/csc-254r.1 · Cited by 25
“Hsf4b has been reported to bind to HSEs under basal condi- tions, but dissociates during stress (Tu et al 2006).”
BackgroundInfluentialZhong, Y., Cheng, H.-Z., Peng, H., et al. (2016) · Oncology Letters · doi:10.3892/ol.2016.5368 · Cited by 25
“Heat shock factors (HSFs) can bind to HSEs, and thus regulate the expression of HSPs (12).”
Lack of heat shock response triggers programmed cell death in a rat histiocytic cell line
Sreedhar, A. S., Pardhasaradhi, B. V. V., Begum, Z., et al. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00970-9 · Cited by 25
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Differential Induction of Hsp70-encoding Genes in Human Hematopoietic Cells
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“This led to the assumption that the C-terminal activation domain would similarly lack structure.(42) HowFig.”
BackgroundThe subapical compartment and its role in intracellular trafficking and cell polarity
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BackgroundExploring HSP90 as a Biomarker for Marine Heatwaves in Pinctada maxima
Masanja, F., Xu, Y., He, G., Feilong, L., Liu, X., Yang, K., Mkuye, R., Liang, J., Deng, Y., & Zhao, L. (2022) · Frontiers in Marine Science · doi:10.3389/fmars.2022.913920 · Cited by 24
“Interestingly, further research on the molecular basis of how HSP90 was activated under heat stress revealed that trans activations of heat shock proteins were mediated via the heat shock factor 1 (HSF1) and heat shock elements (HSE) interactions (Wu, 1995).”
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“Among the five domains, the DBD and OD are the most conserved [8].”
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“The HSR is regulated mainly at the level of transcription by heat shock transcription factor 1 (HSF1; Wu, 1995; Morimoto, 1998; Pirkkala et al. 2001).”
BackgroundIntracellular antigens as targets for antibody based immunotherapy of malignant diseases
Wang, Y., Wang, X., Ferrone, C. R., Schwab, J. H., & Ferrone, S. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2015.10.019 · Cited by 24
“Activated HSF1 binds to the heat shock elements within the promoters of HSP genes and triggers their transcription (Wu, 1995; Zou et al., 1998).”
BackgroundProteomic identification of radiation response markers in mouse intestine and brain
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“Since HSP5, HSP90-b, and HSP1 belong to the HSP family, members of which can response non-selectively to other stresses, such as, heat shock, hypoxia, ethanol, and arsenite [8, 9], we focused on TA1 and PGK1.”
BackgroundIdentification of methyl jasmonate-responsive genes in sugarcane using cDNA arrays
Rosa, V. E. D., Nogueira, F. T. S., Menossi, M., Ulian, E. C., & Arruda, P. (2005) · Brazilian Journal of Plant Physiology · doi:10.1590/s1677-04202005000100014 · Cited by 24
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“This was unexpected given HSF1 is constitutively expressed in most tissues and cell types and appears to be regulated mainly via post-translational mechanisms (Wu 1995).”
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“Heat shock factor 1 (HSF1), a heat (stress)-activated transcription factor, is a critical player in the stress response required for the expression of heat shock proteins (HSPs) (Calderwood et al., 2010; Wu, 1995).”
Padmini, E., Uthra, V., & Lavanya, S. (2012) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-012-9371-0 · Cited by 24
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Xenopus Heat Shock Factor 1 Is a Nuclear Protein before Heat Stress
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Pathology-Dependent Effects Linked to Small Heat Shock Proteins Expression: An Update
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“Indeed, following posttranslational modi�cations and homotrimer formation [9, 10], cytoplasmic HSF1 is activated [11] and migrates into the nucleus to induce a massive transcription of Hsp genes [12, 13].”
BackgroundInfluentialvan Wijk, S. W., Ramos, K. S., & Brundel, B. J. J. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22010442 · Cited by 23
“This evolutionarily conserved transcription factor becomes trimerized and phosphorylated upon activation while being transported to the nucleus, where it targets heat-shock-responsive DNA elements (HSEs) in order to upregulate the HSP genes (Figure 1) [20,21].”
BackgroundMiles, J., Townend, S., Milonaitytė, D., Smith, W., Hodge, F., Westhead, D. R., & van Oosten‐Hawle, P. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3001605 · Cited by 25
“Knockdown or inhibition of Hsp90 activity is known to activate HSF-1–mediated expression of heat-inducible Hsp70 [24,25].”
Cui, J., Tian, H., & Chen, G. (2015) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2015.03.021 · Cited by 23
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“Previous studies have indicated that the dramatic increase in HSP expression is a key part of the heat shock response, which is primarily controlled by HSFs (27,28).”
Benderska, N., Ivanovska, J., Rau, T. T., Schulze‐Luehrmann, J., Mohan, S., Chakilam, S., Gandesiri, M., Ziesché, E., Fischer, T., Söder, S., et al. (2014) · Journal of Cell Science · doi:10.1242/jcs.157024 · Cited by 23
“Because we suggested that HSF1 as transcription factor can switch from a pro-survival to a pro-apoptotic pathway, we next tested the expression level of known HSF1 target genes, such as HSP70, HSP90 and BAG3 (Jacobs and Marnett, 2009; Morimoto et al., 1996; Wu, 1995).”
BackgroundInfluentialTsukao, Y., Yamasaki, M., Miyazaki, Y., et al. (2017) · Oncology Letters · doi:10.3892/ol.2017.5637 · Cited by 23
“Hsp expression is regulated by HSF1, which can bind to the 5' promoter regions of all Hsp genes, and trigger their immediate and massive transcription (19,20).”
Effects of niacin and betaine on bovine mammary and uterine cells exposed to thermal shock in vitro
Xiao, Y., Rungruang, S., Hall, L. W., et al. (2017) · Journal of Dairy Science · doi:10.3168/jds.2016-11876 · Cited by 23
de Almeida, L. D., Quaglio, A. E. V., Costa, C. A. R. D. A., & Stasi, L. C. D. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i24.4369 · Cited by 23
Xin, H., Zhang, H., Zhong, X., Lian, Q., Dong, A., Cao, L., Yi, M., & Cong, R. (2017) · Plant Cell Tissue and Organ Culture (PCTOC) · doi:10.1007/s11240-017-1251-2 · Cited by 22
Isolation and Characterization of the Heat Shock RNA 1
Shamovsky, I., & Nudler, E. (2009) · Methods in molecular biology · doi:10.1007/978-1-59745-558-9_19 · Cited by 23
Differential gene expression in neutrophils from patients with generalized aggressive periodontitis
Kubota, T., Morozumi, T., Shimizu, K., et al. (2001) · Journal of Periodontal Research · doi:10.1034/j.1600-0765.2001.360607.x · Cited by 23
Structural and functional analysis of the Entamoeba histolytica EhrabB gene promoter
Romero-Díaz, M., Gómez, C., López-Reyes, I., Martínez, M. B., Orozco, E., & Rodríguez, M. A. (2007) · BMC Molecular Biology · doi:10.1186/1471-2199-8-82 · Cited by 23
“Comparative analyses of the 5'-flanking region of genes induced by heat shock have revealed that they contain tracts with three or more nGAAn or nTTCn sequences, which are essential for heat induction response [36].”
BackgroundYuan, J., Xiao, L., Lu, C., et al. (2009) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-7-23 · Cited by 23
Targeted Deletion of Hsf1, 2, and 4 Genes in Mice
Jin, X., Eroglu, B., Moskophidis, D., et al. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7477-1_1 · Cited by 23
“In our targeting strategy, we selected to delete a portion of the exon 2 of the hsf1 gene for the reasons provided below: (1) In the hsf1 gene, exon 1 is located 18 kb apart from other exons.”
Plant heat shock transcription factors: positive and negative aspects of regulation
Czarnecka‐Verner, E., Yuan, C., Nover, L., et al. (1997) · Acta Physiologiae Plantarum · doi:10.1007/s11738-997-0050-5 · Cited by 23
Full-field electroretinograms in miniature poodles with progressive rod-cone degeneration.
Sandberg, M. A., Pawlyk, B. S., & Berson, E. L. (1986) · PubMed · Cited by 23
Schiavone, S., Morgese, M. G., Tucci, P., & Trabace, L. (2021) · Molecules · doi:10.3390/molecules26154700 · Cited by 26
Expression of Hsf1, Hsf2, and Phlda1 in cells undergoing cryptorchid‐induced apoptosis in rat testes
Liu, F., Xu, Z., Qian, X., et al. (2011) · Molecular Reproduction and Development · doi:10.1002/mrd.21304 · Cited by 22
“In vertebrates, there are four Hsfs: Hsf1, Hsf2, Hsf3, and Hsf4 (Wu, 1995; Morimoto, 1998; Fujimoto et al., 2010).”
Ashraf, S., Shah, S. M. A., Saini, N., et al. (2014) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-014-0275-3 · Cited by 22
“Members of the HSF family (HSF1, HSF2, HSF3 and HSF4) bind to heat shock elements in the promoters of Hsp genes and regulate their transcription [43, 44].”
BackgroundZheng, G., Dong, S., Hou, Y., et al. (2012) · Aquaculture · doi:10.1016/j.aquaculture.2012.06.002 · Cited by 22
“In eukaryotes, the dramatic up-regulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF) binding specifically to heat shock promoter elements (HSE) (Wu, 1995).”
Background
Metadata
- Authors
- Wu, C.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Wu, Carl
- ORCID
- Wu, Carl
- Venue
- Annual Review of Cell and Developmental Biology
- Publisher
- Annual Reviews
- Published
- 1995-11
- Volume
- 11
- Issue
- 1
- Pages
- 441-469
- ISSN
- 1081-0706 (ISSN-L)
- 1530-8995
- OpenAlex
- W2145760315
- Cited by
- 1,231
- References
- 0
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 29 · 2023: 20 · 2022: 32 · 2021: 33 · 2020: 23 · 2019: 35 · 2018: 35 · 2017: 31 · 2016: 40 · 2015: 48 · 2014: 44 · 2013: 49 · 2012: 57
- FWCI
- 11.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- heat shock transcription factor, heat shock proteins, heat shock gene expression, DNA binding, transcriptional activation
- MeSH terms
- Heat Shock Transcription Factors, Amino Acid Sequence, Animals, Bacteria, Binding Sites, Cloning, Molecular, DNA-Binding Proteins, Heat-Shock Proteins, Humans, Models, Structural, Molecular Sequence Data, Transcription Factors, Conserved Sequence, Sequence Homology, Amino Acid, Protein Structure, Secondary, Helix-Turn-Helix Motifs
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