First Author | Chao C | Year | 2000 |
Journal | Proc Natl Acad Sci U S A | Volume | 97 |
Issue | 22 | Pages | 11936-41 |
PubMed ID | 11035798 | Mgi Jnum | J:86520 |
Mgi Id | MGI:2680506 | Doi | 10.1073/pnas.220252297 |
Citation | Chao C, et al. (2000) Phosphorylation of murine p53 at ser-18 regulates the p53 responses to DNA damage. Proc Natl Acad Sci U S A 97(22):11936-41 |
abstractText | Ser-15 of human p53 (corresponding to Ser-18 of mouse p53) is phosphorylated by ataxia-telangiectasia mutated (ATM) family kinases in response to ionizing radiation (IR) and UV light. To determine the effects of phosphorylation of endogenous murine p53 at Ser-18 on biological responses to DNA damage, we introduced a missense mutation (Ser-18 to Ala) by homologous recombination into both alleles of the endogenous p53 gene in mouse embryonic stem (ES) cells. Our analyses showed that phosphorylation of murine p53 at Ser-18 in response to IR or UV radiation was required for a full p53-mediated response to these DNA damage-inducing agents. In contrast, phosphorylation of p53 at Ser-18 was not required for ATM-dependent cellular resistance after exposure to IR. Additionally, efficient acetylation of the C terminus of p53 in response to DNA damage did not require phosphorylation of murine p53 at Ser-18. |