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

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

Research output: Contribution to journalArticlepeer-review

471 Scopus citations

Abstract

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 (US)
Pages (from-to)1063-1066
Number of pages4
JournalScience
Volume323
Issue number5917
DOIs
StatePublished - Feb 20 2009

ASJC Scopus subject areas

  • General

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