FOXO transcription factors have important roles in metabolism, cellular 
proliferation, stress tolerance, and aging. FOXOs are negatively regulated by 
protein kinase B/c-Akt-mediated phosphorylation. Here we show that FOXO factors 
are also subject to regulation by reversible acetylation. We provide evidence 
that the acetyltransferase CREB-binding protein (CBP) binds FOXO resulting in 
acetylation of FOXO. This acetylation inhibits FOXO transcriptional activity. 
Binding of CBP and acetylation are induced after treatment of cells with 
peroxide stress. Deacetylation of FOXOs involves binding of the NAD-dependent 
deacetylase hSir2(SIRT1). Accordingly, hSir2(SIRT1)-mediated deacetylation 
precludes FOXO inhibition through acetylation and thereby prolongs 
FOXO-dependent transcription of stress-regulating genes. These data demonstrate 
that acetylation functions in a second pathway of negative control for FOXO 
factors and provides a novel mechanism whereby hSir2(SIRT1) can promote cellular 
survival and increase lifespan.