Control of apoptosis and mitotic spindle checkpoint by survivin.
Li, Fengzhi; Ambrosini, Grazia; Chu, Emily Y.; Plescia, Janet; Tognin, Simona; Marchisio, Pier Carlo; Altieri, Dario C.
[Letter]
Nature.
396(6711):580-584, December 10, 1998.
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Progression of the cell cycle and control of apoptosis (programmed cell death) are thought to be intimately linked processes [1], acting to preserve homeostasis and developmental morphogenesis [2].Although proteins that regulate apoptosis have been implicated in restraining cell-cycle entry [3] and controlling ploidy (chromosome number) [4], 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 [5,6], survivin [7], 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 [8]. 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 [7] may overcome this apoptotic checkpoint and favour aberrant progression of transformed cells through mitosis.
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