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 response that is evolutionarily conserved from S. cerevisiae (Hsf1) to mammals (HSF1/2).
“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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“Subsequent studies showed that, in contrast to a single HSF in invertebrates, multiple HSFs are expressed in plants and vertebrate”
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“Hsp transcription requires activated heat shock transcription factor 1 (hsf1), which is itself overexpressed in cancer and plays a role in invasion and metastasis (Wu 1995; McMillan et al 1998; Hoang et al 2000; Wang et al 2004).”
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BackgroundInfluentialHeat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update
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“depends on the activity of a unique transcription factor—heat shock factor 1 (HSF1)—that can bind to the 50promoter regions of all HSP genes and trigger instantaneous and massive transcription of these stress protein genes (Wu 1995; Calderwood et al. 2010).”
Scharf, K., Heider, H., Höhfeld, I., et al. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.4.2240 · Cited by 258 · see citing works
Nutritional Interventions to Alleviate the Negative Consequences of Heat Stress
Rhoads, R. P., Baumgard, L. H., Suagee, J. K., & Sanders, S. R. (2013) · Advances in Nutrition · doi:10.3945/an.112.003376 · Cited by 261 · see citing works
Kurucz, I., Morva, Á., Vaag, A. A., Eriksson, K., Huang, X., Groop, L., & Koranyi, L. I. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1102 · Cited by 254 · see citing works
“The magnitude of the difference between Hsp-72 mRNA levels of the healthy and diabetic groups (10-fold) in our experiments, and the fact that stress protein expression in general is strongly regulated at the level of transcription (28,29), support the idea that in this case as well the differences in the levels of tra…”
BackgroundChaperone Regulation of the Heat Shock Protein Response
Voellmy, R. W., & Boellmann, F. (2007) · Springer eBooks · doi:10.1007/978-0-387-39975-1_9 · Cited by 252 · see citing works
The Stress of Protein Misfolding: From Single Cells to Multicellular OrganismsPreprint
Gidalevitz, T., Prahlad, V., & Morimoto, R. I. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009704 · Cited by 254 · see citing works
“2 and 3) (Wu 1995; Morimoto 1998).”
BackgroundInfluentialHSF4 is required for normal cell growth and differentiation during mouse lens development
Fujimoto, M., Izu, H., Seki, K., Fukuda, K., Nishida, T., Yamada, S., Kato, K., Yonemura, S., Inouye, S., & Nakai, A. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600435 · Cited by 252 · see citing works
“tion factor (HSF), which binds to a heat shock element (HSE), which is composed of at least three inverted repeats of consensus sequence nGAAn ( Wu, 1995 ).”
BackgroundJohnson, J. D., & Fleshner, M. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0905523 · Cited by 251 · see citing works
“The gene for Hsp72 contains at least two regulatory elements that interact with heat shock transcription factors (HSFs) [9, 10].”
BackgroundThe heat shock factor family and adaptation to proteotoxic stress
Fujimoto, M., & Nakai, A. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07827.x · Cited by 242 · see citing works
Hsp70 and Its Molecular Role in Nervous System Diseases
Turturici, G., Sconzo, G., & Geraci, F. (2011) · Biochemistry Research International · doi:10.1155/2011/618127 · Cited by 247 · see citing works
“Experimental data suggest that manipulation of the cellular stress response may offer strategies to protect the brain during progression of neurodegenerative disease.”
BackgroundNishizawa‐Yokoi, A., Nosaka, R., Hayashi, H., et al. (2011) · Plant and Cell Physiology · doi:10.1093/pcp/pcr045 · Cited by 247 · see citing works
“Hsf acts through a highly conserved heat shock element (HSE) that contains at least three 50-nGAAn-30 repeats in alternating orientations in the promoters of HS-inducible genes of all eukaryotes (Wu 1995, Schöffl et al. 1998).”
Östling, P., Björk, J., Roos‐Mattjus, P., Mezger, V., & Sistonen, L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607556200 · Cited by 238 · see citing works
Winkler, A., Arkind, C., Mattison, C. P., Burkholder, A. C., Knoche, K., & Ota, I. M. (2002) · Eukaryotic Cell · doi:10.1128/ec.1.2.163-173.2002 · Cited by 241 · see citing works
“For example, heat stress induces heat shock transcription factor to trimerize into its active form (43), while the Salmonella transcriptional repressor, TlpA, undergoes a heat-induced transition from an active dimer to an inactive monomer (12).”
BackgroundYoshida, T., Sakuma, Y., Todaka, D., et al. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.01.134 · Cited by 244 · see citing works
“The HSE sequence (nGAAnnTTCn or nTTCnnGAAn) [18], which is a recognition sequence of HSFs, was found in the 1000-bp promoter region of 15 genes among these 20 up-regulated genes.”
BackgroundYan, L.-J., Christians, E., Liu, L., Xiao, X., Sohal, R., & Benjamin, I. (2002) · EMBO Journal · doi:10.1093/emboj/cdf528 · Cited by 258 · see citing works
Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation
Zheng, X., Krakowiak, J., Patel, N., Ali Beyzavi, B., Ezike, J., Khalil, A. S., & Pincus, D. (2016) · eLife · doi:10.7554/elife.18638 · Cited by 245 · see citing works
“DNA interactions known, having been maintained since the last common ancestor of the eukaryotic lineage (Wu, 1995).”
BackgroundSopinka, N., Donaldson, M., O’Connor, C. M., Suski, C. D., & Cooke, S. J. (2016) · Fish physiology · doi:10.1016/b978-0-12-802728-8.00011-4 · Cited by 256 · see citing works
“The damaged and ubiquitinated protein in the cell induces a heat shock response, aimed at repairing protein damage (Wu, 1995).”
BackgroundLiu, H., & Charng, Y. (2013) · PLANT PHYSIOLOGY · doi:10.1104/pp.113.221168 · Cited by 231 · see citing works
“HSFs are characterized by a DNA-binding domain and hydrophobic heptad repeat regions (Wu, 1995; Morimoto, 1998; Åkerfelt et al., 2010).”
BackgroundNegative regulation of the heat shock transcriptional response by HSBP1Preprint
Satyal, S. H., Chen, D., Fox, S. G., Kramer, J. M., & Morimoto, R. I. (1998) · Genes & Development · doi:10.1101/gad.12.13.1962 · Cited by 225 · see citing works
“The elevated expression of genes encoding heat shock proteins in response to environmental and physiological stress is mediated by heat shock factor (HSF), an inducible transcriptional activator that is ubiquitously expressed in all organisms from yeast to humans and is essential for the inducible transcriptional resp…”
BackgroundChromatin Landscape Dictates HSF Binding to Target DNA Elements
Guertin, M. J., & Lis, J. T. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001114 · Cited by 228 · see citing works
“are an attractive model system to study the general functions of HSF and its induced transcriptional regulation”
BackgroundHEAT SHOCK RESPONSE AND AGEING: MECHANISMS AND APPLICATIONS
Verbeke, P., Fonager, J., Clark, B. F. C., & Rattan, S. I. S. (2001) · Cell Biology International · doi:10.1006/cbir.2001.0789 · Cited by 220 · see citing works
Guo, Y., Guettouche, T., Fenna, M., Boellmann, F., Pratt, W. B., Toft, D. O., Smith, D. F., & Voellmy, R. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105931200 · Cited by 221 · see citing works
- 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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