Abstrakti
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.
Alkuperäiskieli | Englanti |
---|---|
Sivut | 1063-6 |
Sivumäärä | 4 |
Julkaisu | Science |
Vuosikerta | 323 |
Numero | 5917 |
DOI - pysyväislinkit | |
Tila | Julkaistu - 20 helmik. 2009 |
OKM-julkaisutyyppi | A1 Julkaistu artikkeli, soviteltu |