Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells.
Survivin, one of the most tumor-specific gene products, has been implicated in both anti-apoptosis and cytokinesis. However, the mechanism by which survivin regulates these two different processes is still elusive. Here, we show that survivin binds to the catalytic domain of Aurora-B. We demonstrate that in the presence of survivin, Aurora-B phosphorylates histone H3 much more efficiently than in the absence of survivin in a cell-free system. Furthermore, we confirm that cells lacking survivin due to survivin antisense oligonucleotide-treatment have lower Aurora-B kinase activity, whereas cells overexpressing survivin have higher Aurora-B kinase activity. We also provide evidence that depletion of survivin by survivin antisense oligonucleotide treatment causes significant reduction of endogenous phosphorylated histone H3 and mislocalization of Aurora-B. These results indicate that survivin stimulates Aurora-B kinase activity and helps correctly target Aurora-B to its substrates during the cell cycle, thus providing a mechanism as to how survivin exerts its function in human cells.
Chen
Jun
J
Abbott Laboratories, Cancer Research, AP10-1, Abbott Park, Illinois 60064, USA. jun.chen@abbott.com
Jin
Sha
S
Tahir
Stephen K
SK
Zhang
Haichao
H
Liu
Xuesong
X
Sarthy
Aparna V
AV
McGonigal
Thomas P
TP
Liu
Zhihong
Z
Rosenberg
Saul H
SH
Ng
Shi-Chung
SC
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D020134:Catalytic Domain; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000077022:Survivin
C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D006657:Histones; D051034:Inhibitor of Apoptosis Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases