Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1

Sandy D Westerheide, Julius Anckar, Stanley M Stevens, Lea Sistonen, Richard I Morimoto

Research output: Contribution to journalArticleScientificpeer-review


Heat shock factor 1 (HSF1) is essential for protecting cells from protein-damaging stress associated with misfolded proteins and regulates the insulin-signaling pathway and aging. Here, we show that human HSF1 is inducibly acetylated at a critical residue that negatively regulates DNA binding activity. Activation of the deacetylase and longevity factor SIRT1 prolonged HSF1 binding to the heat shock promoter Hsp70 by maintaining HSF1 in a deacetylated, DNA-binding competent state. Conversely, down-regulation of SIRT1 accelerated the attenuation of the heat shock response (HSR) and release of HSF1 from its cognate promoter elements. These results provide a mechanistic basis for the requirement of HSF1 in the regulation of life span and establish a role for SIRT1 in protein homeostasis and the HSR.

Original languageEnglish
Pages (from-to)1063-6
Number of pages4
Issue number5917
Publication statusPublished - 20 Feb 2009
MoE publication typeA1 Journal article-refereed


  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Cellular Senescence/physiology
  • Chromatin Immunoprecipitation
  • DNA/metabolism
  • DNA-Binding Proteins/metabolism
  • Down-Regulation
  • HSP70 Heat-Shock Proteins/genetics
  • HeLa Cells
  • Heat Shock Transcription Factors
  • Heat-Shock Response
  • Homeostasis
  • Humans
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA, Small Interfering
  • Sirtuin 1
  • Sirtuins/genetics
  • Stress, Psychological
  • Transcription Factors/metabolism
  • Transfection


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