title: Palmdelphin, a novel target of p53 with Ser46 phosphorylation, controls cell death in response to DNA damage.
abstract: The tumor suppressor gene p53 regulates apoptosis in response to DNA damage. Promoter selectivity of p53 depends on mainly its phosphorylation. Particularly, the phosphorylation at serine-46 of p53 is indispensable in promoting pro-apoptotic genes that are, however, poorly determined. In the current study, we identified palmdelphin as a pro-apoptotic gene induced by p53 in a phosphorylated serine-46-specific manner. Upregulation of palmdelphin was observed in wild-type p53-transfected cells, but not in serine-46-mutated cells. Expression of palmdelphin was induced by p53 in response to DNA damage. In turn, palmdelphin induced apoptosis. Intriguingly, downregulation of palmdelphin resulted in necroptosis-like cell death via ATP depletion. Upon DNA damage, palmdelphin dominantly accumulated in the nucleus to induce apoptosis. These findings define palmdelphin as a target of serine-46-phosphorylated p53 that controls cell death in response to DNA damage.
authors.affiliation: 1] Department of Biochemistry, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Japan [2] Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Dashzeveg
authors.affiliation: Department of Biochemistry, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Taira
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.
authors.forename: Z-G
authors.initials: ZG
authors.lastname: Lu
authors.affiliation: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kimura
authors.affiliation: Department of Biochemistry, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009336:Necrosis; D010766:Phosphorylation; D034622:RNA Interference; D012694:Serine; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; C443110:PALMD protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D012694:Serine; D000255:Adenosine Triphosphate