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Science 323 (5917): 1063-1066

Copyright © 2009 by the American Association for the Advancement of Science

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

Sandy D. Westerheide,1* Julius Anckar,2* Stanley M. Stevens, Jr.,3 Lea Sistonen,2 Richard I. Morimoto1{dagger}

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.

1 Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL, 60208, USA.
2 Department of Biology, Turku Centre for Biotechnology, Åbo Akademi University, FI-20520 Turku, Finland.
3 University of Florida, Protein Chemistry Core Facility, Interdisciplinary Center for Biotechnology Research, Gainesville, FL 32610, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: r-morimoto{at}

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