The Bcl-2 family in apoptosis. (A) The conserved function of the Bcl-2 family in apoptosis regulation. A linear apoptotic pathway with a single gene at each step is genetically defined in C. elegans, with the Bcl-2 family of proteins as upstream regulators.9 EGL-1, the only BH3-only protein in C. elegans, is required for all developmental cell death in this organism. EGL-1 binds to the Bcl-2 homologue CED-9 to free ATPase and Apaf-1 homolog CED-4, leading to its assembly into the apoptosome to activate the caspase, CED-3. A similar pathway has been defined in mammalian cells. The Bcl-2 members have expanded greatly from 2 in C. elegans to 25, with over 10 BH3-only proteins, 5 Bcl-2 like proteins and 3 Bax-like proteins in mouse and human. (B) The Bcl-2 family is structurally and functionally divided into three groups in mammals. The Bax-like group is absent in C. elegans.