Caspase regulation during apoptosis

A key event in the initiation of apoptosis is the activation of a cascade of cysteine-aspartate specific proteases known as caspases.



Functional homologues of caspases and caspase regulators across species are indicated by the same colour. Caspase-9 in mammals and Dronc in the fruitfly Drosophila melanogaster are initiator caspases, whereas caspase-3 and -7 in mammals and Drice in fruitflies belong to the class of effector caspases. CED-3 (cell-death abnormality-3) in the nematode worm Caenorhabditis elegans functions both as an initiator and effector caspase. The inhibitor of apoptosis (IAP) proteins suppress apoptosis by negatively regulating the caspases, whereas SMAC (second mitochondria-derived activator of caspases)/DIABLO (direct IAP-binding protein with low pI) in mammals and the RHG proteins Reaper, Hid, Grim and Sickle in fruitflies can remove the IAP-mediated negative regulation of caspases. AIF, apoptosis-inducing factor; APAF1, apoptotic-protease-activating factor-1; Cyt c, cytochrome c; EndoG, endonuclease G; HTRA2, high-temperature-requirement protein A2.