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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Westerheide SD, Anckar J, Stevens SM, Sistonen L, Morimoto RI
Publiceringsår: 2009
Tidskrift: Science
Tidskriftsakronym: SCIENCE
Volym: 323
Nummer: 5917
Artikelns första sida, sidnummer: 1063
Artikelns sista sida, sidnummer: 1066
Antal sidor: 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.

Senast uppdaterad 2019-19-10 vid 04:07