Human Sir2 and the 'silencing' of p53 activity.
Members of the evolutionarily conserved silent information regulator 2 (Sir2) protein family are nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylases. In yeast, the founding Sir2 protein is known to function in transcriptional silencing processes through the deacetylation of histones H3 and H4, thus setting up a repressive chromatin structure. Yeast and Caenorhabditis elegans Sir2 are also involved in regulating the life span of these organisms. Until recently, the function of mammalian Sir2 family members was completely unknown. However, several recent studies have now determined a remarkable function for the human SIRT1 protein, which is the closest human homolog of yeast Sir2. SIRT1 specifically associates with the p53 tumor suppressor protein and deacetylates it, resulting in negative regulation of p53-mediated transcriptional activation. Importantly, p53 deacetylation by SIRT1 also prevents cellular senescence and apoptosis induced by DNA damage and stress.
Smith
Jeffrey
J
Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Jordan Hall, Box 800733, Charlottesville, VA 22908, USA. jss5y@virginia.edu
D000818:Animals; D004249:DNA Damage; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D016159:Tumor Suppressor Protein p53; D009243:NAD; C087778:SIR2 protein, S cerevisiae; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases