Phosphorylation of p53 serine 15 increases interaction with CBP

p53 exerts its cell cycle regulatory effects through its ability to functio n as a sequence-specific DNA binding transcription factor. CREB-binding pro tein (CBP)/p300, through its interaction with the N terminus of p53, acts a s a coactivator for p53 and increases the sequence-specific DNA-binding act ivity of p53 by acetylating its C terminus. The same N-terminal domain of p 53 has recently been shown to be phosphorylated at Ser(15) in response to g amma-irradiation. Remarkably, we now demonstrate that phosphorylation of p5 3 at Ser(15) increases its ability to recruit CBP/p300. The increase in CBP /p300 binding was followed by an increase in the overall level of acetylati on of the C terminus of p53. These results provide a mechanism for the acti vation of p53-regulated genes following DNA damage, through a signaling pat hway linking p53 N-terminal kinase and C-terminal acetyltransferase activit ies.