Rethinking HSF1 in Stress, Development, and Organismal Health

Jian Li, Johnathan Labbadia, Richard I. Morimoto*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

164 Scopus citations


The heat shock response (HSR) was originally discovered as a transcriptional response to elevated temperature shock and led to the identification of heat shock proteins and heat shock factor 1 (HSF1). Since then HSF1 has been shown to be important for combating other forms of environmental perturbations as well as genetic variations that cause proteotoxic stress. The HSR has long been thought to be an absolute response to conditions of cell stress and the primary mechanism by which HSF1 promotes organismal health by preventing protein aggregation and subsequent proteome imbalance. Accumulating evidence now shows that HSF1, the central player in the HSR, is regulated according to specific cellular requirements through cell-autonomous and non-autonomous signals, and directs transcriptional programs distinct from the HSR during development and in carcinogenesis. We discuss here these ‘non-canonical’ roles of HSF1, its regulation in diverse conditions of development, reproduction, metabolism, and aging, and posit that HSF1 serves to integrate diverse biological and pathological responses. The activity of HSF1 in response to heat shock and other forms of cell stress conditions is tuned to the proliferative and metabolic status of the cell. The HSR can be regulated in a cell non-autonomous manner through intertissue signaling to communicate stress signals and to ensure a coordinated organismal wide proteostatic response. During development and in carcinogenesis, HSF1 directs transcriptional programs that are distinct from the HSR. The transcriptional regulatory mechanism employed by HSF1 in development is uncoupled from the HSR through partnership with other transcription factors.

Original languageEnglish (US)
Pages (from-to)895-905
Number of pages11
JournalTrends in Cell Biology
Issue number12
StatePublished - Dec 2017


  • HSF1
  • cell proliferation
  • heat shock response (HSR)
  • metabolism
  • organismal health
  • proteostasis

ASJC Scopus subject areas

  • Cell Biology


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