SIRT1, the human homolog of the S. cerevisiae Sir2 protein, functions as an NAD-dependent deacetylase of a number of nonhistone substrates including p53. In response to DNA damage, SIRT1 binds and deacetylates the p53 protein at c-terminal Lys382 residue and attenuate p53-mediated functions. When overexpressed in mouse embryo fibroblasts, SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. In mammalian cells, SIRT1 appears to control the cellular response to stress by regulating the FOXO family of forkhead transcription factors. The Poly6343 antibody has been shown to be useful for western blotting and immunoprecipitation of human SIRT1 protein.