Regulation of p53 activity through lysine

p53isatumoursuppressorthatregulatesthecellularresponsetogenotoxicstresses.p53isashort-livedproteinanditsactivityisregulated mostly by stabilization via different post-translational modifications. Here we report a novel mechanism of p53regulation through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within thecarboxyl-terminus regulatory region. Methylated p53 is restricted to the nucleus and the modification positively affects itsstability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystalstructureofaternarycomplexofSet9withap53peptideandthecofactorproductS-adenosyl-