Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53

TLDR

p53 is activated and phosphorylated on serine‑15 by DNA‑damaging agents, with ATM acting upstream in the ionizing‑radiation–induced signaling pathway. ATM functions as a manganese‑dependent kinase that phosphorylates p53 on serine‑15, its activity is rapidly increased by ionizing radiation but not ultraviolet light, and its deficiency in ataxia telangiectasia cells reduces p53 phosphorylation, supporting ATM’s role in vivo.

Abstract

The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo.