| First Author | Chao C | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 42 | Pages | 41028-33 |
| PubMed ID | 12909629 | Mgi Jnum | J:86185 |
| Mgi Id | MGI:2678972 | Doi | 10.1074/jbc.M306938200 |
| Citation | Chao C, et al. (2003) Cell type- and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses. J Biol Chem 278(42):41028-33 |
| abstractText | Phosphorylation of mouse p53 at Ser18 occurs after DNA damage. To determine the physiological roles of this phosphorylation event in p53-dependent DNA damage responses, a Ser18 to Ala missense mutation was introduced into the germline of mice. Thymocytes and fibroblasts from the knock-in mice show reduced transactivation of many p53 target genes following DNA damage. p53 protein stabilization and DNA binding are similar in knock-in and wild type mice, but C-terminal acetylation was defective, consistent with a role for Ser18 in the recruitment of transcriptional co-activators. The apoptotic response of knock-in thymocytes to ionizing radiation is intermediate between that of wild type and p53 null thymocytes. Despite impaired transcriptional and apoptotic responses, the knock-in mice are not prone to spontaneous tumorigenesis. This indicates that neither phosphorylation of p53 on Ser18 by ATM nor a full transcriptional response is essential to prevent spontaneous tumor formation in mice. |
