Cell
Volume 116, Issue 4, 20 February 2004, Pages 551-563
Journal home page for Cell

Article
Mammalian SIRT1 Represses Forkhead Transcription Factors

https://doi.org/10.1016/S0092-8674(04)00126-6Get rights and content
Under an Elsevier user license
open archive

Abstract

The NAD-dependent deacetylase SIR2 and the forkhead transcription factor DAF-16 regulate lifespan in model organisms, such as yeast and C. elegans. Here we show that the mammalian SIR2 ortholog SIRT1 deacetylates and represses the activity of the forkhead transcription factor Foxo3a and other mammalian forkhead factors. This regulation appears to be in the opposite direction from the genetic interaction of SIR2 with forkhead in C. elegans. By restraining mammalian forkhead proteins, SIRT1 also reduces forkhead-dependent apoptosis. The inhibition of forkhead activity by SIRT1 parallels the effect of this deacetylase on the tumor suppressor p53. We speculate how downregulating these two classes of damage-responsive mammalian factors may favor long lifespan under certain environmental conditions, such as calorie restriction.

Cited by (0)

5

These authors contributed equally to this work.