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Many cell death signals induce apoptosis via a conserved pathway of regulators, adaptors, and caspases. In C. elegans, the negative regulator Ced-9 inhibits apoptosis by binding to the adaptor Ced-4. In the absence of inhibition by Ced-9, Ced-4 binds two molecules of the caspase Ced-3, resulting in autocleavage and caspase activation. In mammals, regulators of the Bcl-2 family (Ced-9 homologs) act at the mitochondria to control release of cytochrome c, which is required for the binding of caspase-9 to the adaptor Apaf-1 (the Ced-4 homolog). Release of cytochrome c from mitochondria thus signals the activation of caspase-9, which then activates downstream caspases to induce apoptosis.
