title: Mutation of mouse p53 Ser23 and the response to DNA damage.
abstract: Recent studies have suggested that phosphorylation of human p53 at Ser20 is important for stabilizing p53 in response to DNA damage through disruption of the interaction between MDM2 and p53. To examine the requirement for this DNA damage-induced phosphorylation event in a more physiological setting, we introduced a missense mutation into the endogenous p53 gene of mouse embryonic stem (ES) cells that changes serine 23 (S23), the murine equivalent of human serine 20, to alanine (A). Murine embryonic fibroblasts harboring the p53(S23A) mutation accumulate p53 as well as p21 and Mdm2 proteins to normal levels after DNA damage. Furthermore, ES cells and thymocytes harboring the p53(S23A) mutation also accumulate p53 protein to wild-type levels and undergo p53-dependent apoptosis similarly to wild-type cells after DNA damage. Therefore, phosphorylation of murine p53 at Ser23 is not required for p53 responses to DNA damage induced by UV and ionizing radiation treatment.
authors.affiliation: Section of Molecular Biology, Division of Biology, University of California, San Diego, La Jolla, California 92093-0322, USA.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Wu
authors.forename: John
authors.initials: J
authors.lastname: Earle
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Saito
authors.forename: Carl W
authors.initials: CW
authors.lastname: Anderson
authors.forename: Ettore
authors.initials: E
authors.lastname: Appella
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004249:DNA Damage; D016158:Genes, p53; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D009687:Nuclear Proteins; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2