Cited by 1,231Heat shock proteins researchGenomics and Chromatin DynamicsBacterial Genetics and Biotechnology

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Heat Shock Transcription Factors: Structure and Regulation

Wu, Carl·1995·Annual Review of Cell and Developmental Biology

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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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Crossref · 10.1146/annurev.cb.11.110195.002301

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BackgroundInfluential
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Background
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BackgroundSelf-citation
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Background
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BackgroundInfluential
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Influential
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Background
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Background
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Background
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Background
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Background
Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis
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Background
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Background
Interspecific- and acclimation-induced variation in levels of heat-shock proteins 70 (hsp70) and 90 (hsp90) and heat-shock transcription factor-1 (HSF1) in congeneric marine snails (genusTegula): implications for regulation ofhspgene expression
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“In lower organisms, such as yeast and Drosophila, regulation of the heat shock response is accomplished by a single hsf gene [Wu, 1995].”
BackgroundInfluential
Activation of the Saccharomyces cerevisiae Heat Shock Transcription Factor Under Glucose Starvation Conditions by Snf1 Protein Kinase
Hahn, J., & Thiele, D. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311005200 · Cited by 174
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“A necessary condition for the heat-shock-activated transcription was a binding of the HSF trimer(s) to the sequence of HSE (for review, see Wu, 1995).”
Background
Regulation of the Transcriptional Response to Oxidative Stress in Fungi: Similarities and Differences
Moye-Rowley, S. (2003) · Eukaryotic Cell · doi:10.1128/ec.2.3.381-389.2003 · Cited by 164
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Background
Hsp70 accumulation in chondrocytic cells exposed to high continuous hydrostatic pressure coincides with mRNA stabilization rather than transcriptional activation
Kaarniranta, K., Elo, M. A., Sironen, R. K., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2319 · Cited by 163
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“This is mediated by heat shock transcription factors (Hsfs) which bind to heat shock elements (HSEs), alternatively oriented pentanucleotide 5 -nGAAn-3 units, present in the upstream sequences of diverse Hsp genes and molecular chaperones (Kingston et al., 1987; Wu, 1995).”
Background
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BackgroundInfluential
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BackgroundInfluential
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Background
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BackgroundSelf-citation
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Background
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“[30] Wu, C.”
Background
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“Trimerized HSF further binds to the heat shock element (HSE), a DNA promoter element located upstream of heat shock genes, resulting in the preferential transcription of these genes (29, 30, 41).”
Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27
Gan, N., Wu, Y.-C., Brunet, M., Garrido, C., Chung, F., Dai, C., & Mi, L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152686 · Cited by 143
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“While mammalian HSF1, the stress-responsive mammalian HSF isoform, is regulated at multiple levels including homotrimerization, nuclear accumulation, DNA binding and transactivation (Wu, 1995; Morimoto, 1998; Morano and Thiele, 1999; Pirkkala et al., 2001), yeast Hsf1 is always in the nucleus as a trimer and is engage…”
Background
Patterns of Hsp gene expression in ectothermic marine organisms on small to large biogeographic scales
Hofmann, G. E. (2005) · Integrative and Comparative Biology · doi:10.1093/icb/45.2.247 · Cited by 137
“…factor in model systems, HSF1 is a latent cytoplasmic transcription factor that becomes activated through trimerization in response to stress (Wu, 1995; Morimoto, 1998; Pirkkala et al., 2001; Nollen and Morimoto, 2002); in response to stress, HSF1 binds specifically to the heat-shock element…”
Background
Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis
Solís, E. J., Pandey, J. P., Zheng, X., Jin, D. X., Gupta, P. B., Airoldi, E. M., Pincus, D., & Denic, V. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.021 · Cited by 130
“Hsf1 activity is adjusted to the state of protein folding in the cell (Anckar and Sistonen, 2011; Wu, 1995).”
Background
The Yeast Hsp110 Family Member, Sse1, Is an Hsp90 Cochaperone
Liu, X., Morano, K. A., & Thiele, D. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.38.26654 · Cited by 133
Function and regulation of heat shock factor 2 during mouse embryogenesis
Rallu, M., Loones, M.-T., Lallemand, Y., Morimoto, R. I., Morange, M., & Mezger, V. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2392 · Cited by 135
Phosphorylation of HSF1 by MAPK-Activated Protein Kinase 2 on Serine 121, Inhibits Transcriptional Activity and Promotes HSP90 Binding
Wang, X., Khaleque, A., Zhao, M., Zhong, R., Gaestel, M., & Calderwood, S. K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505822200 · Cited by 133
Transcriptional Regulation of the Antioxidant Protein 2 Gene, a Thiol-specific Antioxidant, by Lens Epithelium-derived Growth Factor to Protect Cells from Oxidative Stress
Fatma, N., Singh, D. P., Shinohara, T., & Chylack, L. T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100733200 · Cited by 134
Insights into Regulation and Function of the Major Stress-Induced hsp70 Molecular Chaperone In Vivo: Analysis of Mice with Targeted Gene Disruption of the hsp70.1 orhsp70.3 Gene
Huang, L., Mivechi, N. F., & Moskophidis, D. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.24.8575-8591.2001 · Cited by 134
“Members of the murine HSF family (HSF1, HSF2, or HSF4) bind to heat shock elements (alternatively oriented pentanucleotide 5 -nGAAn-3 units) in the promoters of hsp genes and regulate their transcription (35, 48).”
Background
Heat shock factor function and regulation in response to cellular stress, growth, and differentiation signals.
Morano, K. A., & Thiele, D. J. (1999) · Europe PMC (PubMed Central) · Cited by 134
Transcription factors GAF and HSF act at distinct regulatory steps to modulate stress-induced gene activationPreprint
Duarte, F. M., Fuda, N. J., Mahat, D. B., Core, L. J., Guertin, M. J., & Lis, J. T. (2016) · Genes & Development · doi:10.1101/gad.284430.116 · Cited by 131
“HSF is essential for the induction of only a small minority of HS-activated genes HSF is the evolutionarily conserved master regulator of the HS response and is essential for the activation of classical HSP genes (Wu 1995).”
Proteasome inhibition leads to the activation of all members of the heat‐shock‐factor family
Kawazoe, Y., Nakai, A., Tanabe, M., & Nagata, K. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2550356.x · Cited by 132
“3 D, b, nuclear accumulation and trimer formation [35].”
Background
EXPERIMENTAL EVOLUTION OF HSP70 EXPRESSION AND THERMOTOLERANCE IN DROSOPHILA MELANOGASTER
Bettencourt, B. R., Feder, M. E., & Cavicchi, S. (1999) · Evolution · doi:10.1111/j.1558-5646.1999.tb03783.x · Cited by 132
Regulation of heat shock genes in isolated hepatocytes from an Antarctic fish,Trematomus bernacchii
Buckley, B. A., Place, S. P., & Hofmann, G. E. (2004) · Journal of Experimental Biology · doi:10.1242/jeb.01219 · Cited by 131
“All inducible hspgenes are regulated by HSF1, a cytoplasmic transcription factor that becomes activated in response to heat stress (Wu, 1995).”
Influential
Temperature sensing in bacterial gene regulation — what it all boils down to
Hurme, R., & Rhen, M. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.01049.x · Cited by 131
“Although HSF has an inherent ability to respond to temperature, there are other factors that regulate its activity, such as Hsp70 (Wu, 1995).”
Background
Combinatorial Interaction of Cis Elements Specifies the Expression of the Arabidopsis AtHsp90-1Gene
Haralampidis, K., Milioni, D., Rigas, S., et al. (2002) · PLANT PHYSIOLOGY · doi:10.1104/pp.004044 · Cited by 128
Essential requirement for both hsf1 and hsf2 transcriptional activity in spermatogenesis and male fertility
Wang, G., Ying, Z., Jin, X., et al. (2004) · genesis · doi:10.1002/gene.20005 · Cited by 128
Structure of human heat-shock transcription factor 1 in complex with DNA
Neudegger, T., Verghese, J., Hayer-Hartl, M. K., Hartl, F. U., & Bracher, A. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3149 · Cited by 127
LEDGF Binds to Heat Shock and Stress-Related Element to Activate the Expression of Stress-Related Genes
Singh, D. P., Fatma, N., Kimura, A., Chylack, L. T., & Shinohara, T. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4887 · Cited by 126
Heat Stress Activates Fission Yeast Spc1/StyI MAPK by a MEKK-Independent Mechanism
Shiozaki, K., Shiozaki, M., & Russell, P. R. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.6.1339 · Cited by 124
“To test whether heat shock-specific activation of Spc1 in wis1DD cells is dependent on de novo protein synthesis induced by the HSF pathway or other distinct pathways, activation of Spc1 upon heat shock was also examined in wis1DD cells in the presence of cycloheximide, a protein synthesis inhibitor .”
Heat stroke and cytokines
Leon, L. R. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)62024-4 · Cited by 127
A stress regulatory network for co‐ordinated activation of proteasome expression mediated by yeast heat shock transcription factor
Hahn, J., Neef, D. W., & Thiele, D. J. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05097.x · Cited by 125
“The overall fundamental structure of HSF and its binding site heat shock element (HSE) are highly conserved from yeast to humans (Wu, 1995; Littlefield and Nelson, 1999).”
Background
A novel hnRNP protein (HAP/SAF-B) enters a subset of hnRNP complexes and relocates in nuclear granules in response to heat shock
Weighardt, F., Cobianchi, F., Cartegni, L., et al. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.10.1465 · Cited by 124
Transcription factor families inferred from genome sequences of photosynthetic stramenopiles
Rayko, E., Maumus, F., Maheswari, U., Jabbari, K., & Bowler, C. (2010) · New Phytologist · doi:10.1111/j.1469-8137.2010.03371.x · Cited by 127
Protective responses in the ischemic myocardium
Williams, R. S., & Benjamin, I. J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11205 · Cited by 123
“Transcriptional control of the protein chaperone defense Synthesis of HSPs is rapidly induced in response to several forms of cell stress, including hyperthermia, hypoxia, ischemia, and mechanical stretch applied to cells or intact organs (27).”
Background
Heat shock factor 1 promotes invasion and metastasis of hepatocellular carcinoma in vitro and in vivo
Fěng, F., Chang, R., & Yang, L. (2011) · Cancer · doi:10.1002/cncr.26482 · Cited by 121
“HSF1 originally was cloned and identified as a master controller of heat shock response (HSR), which is 1 of the most evolutionarily conserved defensive mechanisms against acute exposure to extreme environmental and pathologic conditions.33 HSF1 has a key role in the cellular response leading to the expression of HSP…”
Background
Proteasome Inhibitors MG132 and Lactacystin Hyperphosphorylate HSF1 and Induce hsp70 and hsp27 Expression
Kim, D., Kim, S., & Li, G. C. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9840 · Cited by 121
Regulation of Molecular Chaperone Gene Transcription Involves the Serine Phosphorylation, 14-3-3ε Binding, and Cytoplasmic Sequestration of Heat Shock Factor 1
Wang, X., Grammatikakis, N., Siganou, A., & Calderwood, S. K. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.17.6013-6026.2003 · Cited by 123
“Such HSF1 is monomeric, is constitutively phosphorylated, and lacks the ability to bind the cis-acting heat shock elements (HSEs) located in the promoters of Hsp genes (50, 55).”
Background
Molecular anatomy of BCL6 translocations revealed by long-distance polymerase chain reaction-based assays.
Akasaka, H., Akasaka, T., Kurata, M., Ueda, C., Shimizu, A., Uchiyama, T., & Ohno, H. (2000) · PubMed · Cited by 120
Heat Shock Element Architecture Is an Important Determinant in the Temperature and Transactivation Domain Requirements for Heat Shock Transcription Factor
Santoro, N., Johansson, N., & Thiele, D. J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.11.6340 · Cited by 118
“Isogenic wild-type HSF and HSF(1-583) cells harboring wild-type and mutant CUP1-lacZ fusions were analyzed to ascertain whether HSE1 or HSE2 plays a role in the dependence of CUP1 transcriptional activation on the yHSF CTA.”
BackgroundMethodResultInfluential

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
DOI: 10.1146/annurev.cb.11.110195.002301
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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Heat Shock Transcription Factors: Structure and Regulation

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