The yeast Sir2 protein mediates chromatin silencing through an intrinsic 
NAD-dependent histone deacetylase activity. Sir2 is a conserved protein and was 
recently shown to regulate lifespan extension both in budding yeast and worms. 
Here, we show that SIRT1, the human Sir2 homolog, is recruited to the 
promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon 
overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and 
deacetylates p53, a component of PML nuclear bodies, and it can repress 
p53-mediated transactivation. Moreover, we show that SIRT1 and p53 co-localize 
in nuclear bodies upon PML upregulation. When overexpressed in primary mouse 
embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and 
rescues PML-mediated premature cellular senescence. Taken together, our data 
establish the SIRT1 deacetylase as a novel negative regulator of p53 function 
capable of modulating cellular senescence.