A mechanism coupling cell division and the control of apoptosis.
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.
Allan
Lindsey A
LA
Biomedical Research Centre, University of Dundee, UK.
Clarke
Paul R
PR
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D002455:Cell Division / Q000502:physiology*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004249:DNA Damage; D004789:Enzyme Activation; D008941:Spindle Apparatus / Q000378:metabolism
D061945:Caspase Inhibitors; D019926:Cyclin B; D056744:Cyclin B1; D016203:CDC2 Protein Kinase; D053453:Caspase 9