Regulation of the mammalian heat shock factor 1

FEBS J. 2017 Jun;284(11):1606-1627. doi: 10.1111/febs.13999. Epub 2017 Feb 1.


Living organisms are endowed with the capability to tackle various forms of cellular stress due to the presence of molecular chaperone machinery complexes that are ubiquitous throughout the cell. During conditions of proteotoxic stress, the transcription factor heat shock factor 1 (HSF1) mediates the elevation of heat shock proteins, which are crucial components of the chaperone complex machinery and function to ameliorate protein misfolding and aggregation and restore protein homeostasis. In addition, HSF1 orchestrates a versatile transcriptional programme that includes genes involved in repair and clearance of damaged macromolecules and maintenance of cell structure and metabolism, and provides protection against a broad range of cellular stress mediators, beyond heat shock. Here, we discuss the structure and function of the mammalian HSF1 and its regulation by post-translational modifications (phosphorylation, sumoylation and acetylation), proteasomal degradation, and small-molecule activators and inhibitors.

Keywords: HSF1 activator; HSF1 inhibitor; cytoprotection; hormesis; phytochemical; sulfhydryl reactivity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adaptation, Physiological / genetics
  • Adaptation, Physiological / physiology*
  • Animals
  • DNA-Binding Proteins / agonists
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation*
  • Heat Shock Transcription Factors
  • Hot Temperature
  • Mammals / genetics
  • Mammals / physiology*
  • Models, Molecular
  • Phosphorylation
  • Phylogeny
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Conformation
  • Protein Folding
  • Protein Processing, Post-Translational
  • Stress, Physiological / genetics
  • Stress, Physiological / physiology*
  • Sumoylation
  • Transcription Factors / agonists
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / chemistry
  • Transcription Factors / physiology*
  • Transcription, Genetic


  • DNA-Binding Proteins
  • Heat Shock Transcription Factors
  • Transcription Factors
  • Proteasome Endopeptidase Complex