Palmdelphin,a novel target of p53 with Ser46 phosphorylation,controls cell death in response to DNA damage |
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Authors: | N Dashzeveg N Taira Z-G Lu J Kimura K Yoshida |
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Institution: | 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 |
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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. |
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Keywords: | palmdelphin p53 DNA damage apoptosis |
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