title: Survivin inhibits anti-growth effect of p53 activated by aurora B.
abstract: Genomic instability and apoptosis evasion are hallmarks of cancer, but the molecular mechanisms governing these processes remain elusive. Here, we found that survivin, a member of the apoptosis-inhibiting gene family, and aurora B kinase, a chromosomal passenger protein, were co-overexpressed in the various glioblastoma cell lines and tumors. Notably, exogenous introduction of the aurora B in human BJ cells was shown to decrease cell growth and increase the senescence-associated beta-galactosidase activity by activation of p53 tumor suppressor. However, aurora B overexpression failed to inhibit cell proliferation in BJ and U87MG cells transduced with dominant-negative p53 as well as in p53(-/-) mouse astrocytes. Aurora B was shown to increase centrosome amplification in the p53(-/-) astrocytes. Survivin was shown to induce anchorage-independent growth and inhibit anti-proliferation and drug-sensitive apoptosis caused by aurora B. Overexpression of both survivin and aurora B further accelerated the proliferation of BJ cells. Taken together, the present study indicates that survivin should accelerate tumorigenesis by inhibiting the anti-proliferative effect of p53 tumor suppressor that is activated by aurora B in normal and glioblastoma cells containing intact p53.
authors.affiliation: The Laboratory of Cell Growth and Function Regulation, College of Life and Environmental Sciences, Korea University, Seoul.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Jung
authors.forename: Tae-Kyung
authors.initials: TK
authors.lastname: Kim
authors.forename: Joong-Seob
authors.initials: JS
authors.lastname: Lee
authors.forename: Se-Yeong
authors.initials: SY
authors.lastname: Oh
authors.forename: Sungwook
authors.initials: S
authors.lastname: Kwak
authors.forename: Xun
authors.initials: X
authors.lastname: Jin
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Sohn
authors.forename: Min-Keun
authors.initials: MK
authors.lastname: Song
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Sohn
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Xumin
authors.initials: X
authors.lastname: Pian
authors.forename: Jang-Bo
authors.initials: JB
authors.lastname: Lee
authors.forename: Yong Gu
authors.initials: YG
authors.lastname: Chung
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Choi
authors.forename: Seungkwon
authors.initials: S
authors.lastname: You
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism; D003260:Contact Inhibition / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004789:Enzyme Activation; D017930:Genes, Reporter; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000502:physiology*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: C107489:BIRC5 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases