title: Activation of p53 by sodium selenite switched human leukemia NB4 cells from autophagy to apoptosis.
abstract: It was revealed by our previous research that sodium selenite repressed autophagy accompanied by the induction of apoptosis in human leukemia NB4 cells. The inhibition of autophagy exerted a facilitative effect on apoptosis. In the present study, we further explored the mechanisms underlying the switch from autophagy to apoptosis and elucidated p53 played a key role. Selenite induced phosphorylation of p53 at the vital site Ser15 via p38MAPK and ERK. Subsequently p53 dissociated with its inhibitory protein mouse double minute 2 (MDM2). Meanwhile, the nucleolar protein B23 transferred from the nucleolus to the nucleoplasm and associated with MDM2, probably stabilizing p53. The active p53 participated in the decrease of autophagic protein Beclin-1 and LC-3, as well as activation of apoptosis-related caspases. Furthermore, in p53 mutant U937 leukemia cells, selenite could not elicit such a switch from autophagy to apoptosis, laying emphasis on the crucial role p53 played in this process.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhushi
authors.initials: Z
authors.lastname: Li
authors.forename: Kejian
authors.initials: K
authors.lastname: Shi
authors.forename: Liying
authors.initials: L
authors.lastname: Guan
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Caimin
authors.initials: C
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D010766:Phosphorylation; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*
chemical_list: C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin; D051736:Proto-Oncogene Proteins c-mdm2; D018038:Sodium Selenite