Control of apoptosis and mitotic spindle checkpoint by survivin.
Progression of the cell cycle and control of apoptosis (programmed cell death) are thought to be intimately linked processes, acting to preserve homeostasis and developmental morphogenesis. Although proteins that regulate apoptosis have been implicated in restraining cell-cycle entry and controlling ploidy (chromosome number), the effector molecules at the interface between cell proliferation and cell survival have remained elusive. Here we show that a new inhibitor of apoptosis (IAP) protein, survivin, is expressed in the G2/M phase of the cell cycle in a cycle-regulated manner. At the beginning of mitosis, survivin associates with microtubules of the mitotic spindle in a specific and saturable reaction that is regulated by microtubule dynamics. Disruption of survivin-microtubule interactions results in loss of survivin's anti-apoptosis function and increased caspase-3 activity, a mechanism involved in cell death, during mitosis. These results indicate that survivin may counteract a default induction of apoptosis in G2/M phase. The overexpression of survivin in cancer may overcome this apoptotic checkpoint and favour aberrant progression of transformed cells through mitosis.
Li
F
F
Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
Ambrosini
G
G
Chu
E Y
EY
Plescia
J
J
Tognin
S
S
Marchisio
P C
PC
Altieri
D C
DC
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000502:physiology; D008938:Mitosis / Q000502:physiology; D009154:Mutation; D009363:Neoplasm Proteins; D011506:Proteins / Q000502:physiology*; D008941:Spindle Apparatus / Q000502:physiology*; D000077022:Survivin; D014404:Tubulin / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D000077022:Survivin; D014404:Tubulin; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus