Survivin inhibits anti-growth effect of p53 activated by aurora B.
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.
Jung
Ji-Eun
JE
The Laboratory of Cell Growth and Function Regulation, College of Life and Environmental Sciences, Korea University, Seoul.
Kim
Tae-Kyung
TK
Lee
Joong-Seob
JS
Oh
Se-Yeong
SY
Kwak
Sungwook
S
Jin
Xun
X
Sohn
Jin-Young
JY
Song
Min-Keun
MK
Sohn
Young-Woo
YW
Lee
Soo-Yeon
SY
Pian
Xumin
X
Lee
Jang-Bo
JB
Chung
Yong Gu
YG
Choi
Young Ki
YK
You
Seungkwon
S
Kim
Hyunggee
H
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
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