Regulation of heat shock transcription factors and their roles in physiology and disease

Rocio Gomez-Pastor, Eileen T. Burchfiel, Dennis J. Thiele

Research output: Contribution to journalReview articlepeer-review

410 Scopus citations


The heat shock transcription factors (HSFs) were discovered over 30 years ago as direct transcriptional activators of genes regulated by thermal stress, encoding heat shock proteins. The accepted paradigm posited that HSFs exclusively activate the expression of protein chaperones in response to conditions that cause protein misfolding by recognizing a simple promoter binding site referred to as a heat shock element. However, we now realize that the mammalian family of HSFs comprises proteins that independently or in concert drive combinatorial gene regulation events that activate or repress transcription in different contexts. Advances in our understanding of HSF structure, post-translational modifications and the breadth of HSF-regulated target genes have revealed exciting new mechanisms that modulate HSFs and shed new light on their roles in physiology and pathology. For example, the ability of HSF1 to protect cells from proteotoxicity and cell death is impaired in neurodegenerative diseases but can be exploited by cancer cells to support their growth, survival and metastasis. These new insights into HSF structure, function and regulation should facilitate the development tof new disease therapeutics to manipulate this transcription factor family.

Original languageEnglish (US)
Pages (from-to)4-19
Number of pages16
JournalNature Reviews Molecular Cell Biology
Issue number1
StatePublished - Jan 1 2018

Bibliographical note

Funding Information:
E.T.B. is supported by a Predoctoral Fellowship from the US National Institutes of Health (F31 GM119375-02). R.G.-P. is supported by a Postdoctoral Fellowship from the Huntington’s Disease Society of America Human Biology Project. The authors acknowledge Alex Jaeger for assistance with Figure 2 and the Reviewers for excellent comments and suggestions.

Publisher Copyright:
© 2017 Macmillan Publishers Limited.


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