When cells receive apoptotic stimuli, such as activation of the TNFα/Fas cell surface receptor, caspase 8 activation, Bid processing and its translocation to the mitochondria ensue. As a result mitochondria release cytochrome c which then binds to Apaf-1, the mammalian Ced-4 homologue, together with dATP. The resultant complex recruits caspase 9 leading to its activation. It then cleaves downstream caspases such as caspase 3, 6, and 7, initiating the caspase cascade. Caspase 9 exhibits basal activity. It can be further activated via interaction of its N-terminal prodomain with the activator protein Apaf-1 in the presence of cytochrome c and dATP. Caspases have been implicated in many disorders including cancer, inflammatory disease, neurodegenerative diseases, stroke and myocardial infarction.
