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Distinct P53 Acetylation Cassettes Differentially Influence Gene-Expression Patterns And Cell Fate., Chad D Knights, Jason Catania, Simone Di Giovanni, Selen Muratoglu, Ricardo Perez, Amber Swartzbeck, Andrew A Quong, Xiaojing Zhang, Terry Beerman, Richard Pestell, Maria Laura Avantaggiati

Kimmel Cancer Center Faculty Papers

The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. An open question is whether such posttranslational changes act redundantly or dependently upon one another. We show that a functional interference between specific acetylated and phosphorylated residues of p53 influences cell fate. Acetylation of lysine 320 (K320) prevents phosphorylation of crucial serines in the NH(2)-terminal region of p53; only allows activation of genes containing high-affinity p53 binding sites, such as p21/WAF; and promotes cell survival after DNA damage. In contrast, acetylation of K373 leads to hyperphosphorylation of p53 NH(2)-terminal residues and enhances the interaction with …