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Publication : Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis.

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.
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