title: Ser18 and Ser23 phosphorylation plays synergistic roles in activating p53-dependent neuronal apoptosis.
abstract: Tumor suppressor p53 is required for the neuronal apoptosis in response to DNA double-stranded break (DSB) damage. Posttranslational modifications such as phosphorylation play important roles in activating p53-dependent apoptosis after DNA damage. In support of this notion, our recent studies indicate that Ser18 and Ser23 phosphorylation together plays critical roles in activating p53 apoptotic activities in vivo. Thymocytes derived from p53(S18/23A) mice are essentially resistant to p53-dependent apoptosis after DNA DSB damage. In addition, identical to p53-deficiency, p53(S18/23A) knock-in mutation completely rescues the embryonic lethality of XRCC4(-/-) mice, which die of the massive p53-dependent apoptosis of embryonic neurons likely as a result of accumulated endogenous DNA damage. To dissect the contribution of Ser18 and Ser23 phosphorylation to p53-dependent neuronal apoptosis, we report here that neither p53(S18A) nor p53(S23A) mutation alone can rescue the embryonic lethality of XRCC4(-/-) mice. Therefore, Ser18 and Ser23 phosphorylation plays synergistic and critical roles in activating p53-dependent neuronal apoptosis.
authors.affiliation: Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093-0322, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Song
authors.forename: Connie
authors.initials: C
authors.lastname: Chao
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C511788:XRCC4 protein, mouse; D012694:Serine