First Author | Slee EA | Year | 2013 |
Journal | Sci Rep | Volume | 3 |
Pages | 3105 | PubMed ID | 24173284 |
Mgi Jnum | J:258075 | Mgi Id | MGI:6144212 |
Doi | 10.1038/srep03105 | Citation | Slee EA, et al. (2013) Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis. Sci Rep 3:3105 |
abstractText | The p53 tumour suppressor is activated in response to a wide variety of genotoxic stresses, frequently via post-translational modification. Using a knock in mouse model with a Ser312 to Ala mutation, we show here that phosphorylation of p53 on Ser312 helps to prevent tumour induction by the alkylating agent MNU, which predominantly caused T cell lymphomas. This is consistent with our previous observation that p53(312A/A) mice are more susceptible to X-ray induced tumourigenesis. Phosphorylation on Ser312 aids p53's interaction with E2F1, and enhances p53-mediated apoptosis. Loss of E2F1 alone does not affect tumour susceptibility to MNU, but its absence partially rescues tumour formation in p53(312A/A) mice, thus reflecting the oncogenic properties of E2F1. Our data confirms the participation of Ser312 phosphorylation in tumour suppression by p53. |