Work

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

Year: 2009

Type: article

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.

Source: Science

DOI: 10.1126/science.1165946

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

Institutions: Northwestern University, Åbo Akademi University, University of Florida, Turku Centre for Biotechnology

Language: English

Topic: Heat shock proteins research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute on Aging, National Institute of General Medical Sciences