Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1

A1 Journal article (refereed)

Internal Authors/Editors

Publication Details

List of Authors: Westerheide SD, Anckar J, Stevens SM, Sistonen L, Morimoto RI
Publication year: 2009
Journal: Science
Journal acronym: SCIENCE
Volume number: 323
Issue number: 5917
Start page: 1063
End page: 1066
Number of pages: 4
ISSN: 0036-8075
eISSN: 1095-9203


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.

Last updated on 2020-04-08 at 04:47