Our recent results demonstrate that caspase activation is regulated during the cell cycle, establishing a direct link between the regulation of apoptosis and cell division (Allan and Clarke, 2007). We show that phosphorylation of caspase-9 is critical for the balance between these processes, restraining the initiation of apoptosis during mitosis. This mechanism is likely to be important in determining sensitivity to anti-cancer drugs that target mitotic cells. We propose that regulation of the phosphorylation of caspase-9 during prolonged mitotic arrest may provide a timing mechanism that initiates apoptosis and destroys an aberrant cell if mitosis is not successfully resolved. This mechanism may play an important role in anti-cancer surveillance and might be exploited to improve cell killing by anti-cancer drugs that target mitotic cells.
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