title: Role for p53 in selenium-induced senescence.
abstract: The tumor suppressor p53 and the ataxia-telangiectasia mutated (ATM) kinase play important roles in the senescence response to oncogene activation and DNA damage. It was previously shown that selenium-containing compounds can activate an ATM-dependent senescence response in MRC-5 normal fibroblasts. Here, the shRNA knockdown approach and other DNA damage assays are employed to test the hypothesis that p53 plays a role in selenium-induced senescence. In MRC-5 cells treated with methylseleninic acid (MSeA, 0-10 μM), depletion of p53 hampers senescence-associated expression of β-galactosidase, disrupts the otherwise S and G2/M cell cycle arrest, desensitizes such cells to MSeA treatment, and increases genome instability. Pretreatment with KU55933, an ATM kinase inhibitor, or NU7026, an inhibitor of DNA-dependent protein kinase, desensitizes MSeA cytotoxicity in scrambled but not p53 shRNA MRC-5 cells. These results suggest that p53 is critical for senescence induction in the response of MRC-5 noncancerous cells to selenium compounds.
authors.affiliation: Department of Nutrition and Food Science,  University of Maryland,  College Park, Maryland 20742, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Ryan T Y
authors.initials: RT
authors.lastname: Wu
authors.forename: Thomas T Y
authors.initials: TT
authors.lastname: Wang
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004249:DNA Damage; D006801:Humans; D012643:Selenium / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D012643:Selenium