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 [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.