title: Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Slee
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D008223:Lymphoma / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D016159:Tumor Suppressor Protein p53; D012694:Serine