Caspase-9 cleavage: do you need it

Caspase-9 which is activated by association with the Apaf-1 apoptosome complex cleaves and activates the downstream effector caspases-3 and -7, thereby executing the caspase-cascade and cell death programme. Although, caspase-9 does not need to be cleaved to be active, apoptotic cell death is always accompanied by autocatalytic cleavage and by further downstream effector caspase-dependent cleavage of caspase-9. In this issue of the Biochemical Journal, Denault and co-workers evaluate the role of caspase-3-dependent cleavage of caspase-9 and conclude that this mechanism mainly serves to enhance apoptosis by alleviating XIAP inhibition of the apical caspase.