title: Survivin-2B promotes autophagy by accumulating IKK alpha in the nucleus of selenite-treated NB4 cells.
abstract: Survivin-2B, a known splice variant of survivin, has been reported to promote cell death in some cancer cells, although it keeps prosurvival function in others, and the mechanisms are unclear. In this report, we discovered that selenite, an antitumor agent, switched protective autophagy to apoptosis in NB4 cells. In this process, the level of survivin-2B was decreased and the interaction between IKK alpha and survivin-2B in the nucleus was attenuated, which further led to the decrease of nuclear IKK alpha. As a result, P73, a known transcript factor of UVRAG, was downregulated. Therefore, the expression of UVRAG, one of the initiators of autophagy, was inhibited. The regulatory status of survivin-2B was also proved in NB4 cells after different chemicals' exposure and in other tumor cell lines (Jurkat, HCT116). Finally, experiments in vivo confirmed that the alterations of survivin-2B, IKK alpha, P73 and UVRAG were the same as that in vitro. Taken together, survivin-2B promoted autophagy and further regulated cell death by accumulating and stabilizing IKK alpha in the nucleus.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: K
authors.initials: K
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: An
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Shan
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ci
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: P
authors.identifier: 0000000272690683
authors.initials: P
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: K
authors.initials: K
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Department of Biochemistry and Molecular Biology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Xu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D045325:HCT116 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020887:Selenious Acid / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D009687:Nuclear Proteins; D000077022:Survivin; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C408122:UVRAG protein, human; C496559:CHUK protein, human; D051550:I-kappa B Kinase; D020887:Selenious Acid