Apoptotic protease activating factor 1 (Apaf-1), originally identified as the mammalian homolog of the C. elegans apoptotic regulatory protein CED-4, is an important signaling protein involved in the activation of caspase-9 during apoptosis. Cytosolic Apaf-1 forms a complex with caspase-9 in the presence of cytochrome c and dATP, ultimately leading to caspase-9 activation and subsequent activation of caspase-3. The protein contains an amino-terminal CARD domain, a central CED-4 homology domain, and multiple WD-40 repeats at the carboxy terminus. Several isoforms of Apaf-1 are expressed through alternative splicing generating a small insert following the CARD domain as well as an extra WD-40 repeat. Apaf-1 knock-out mice display widespread defects in apoptosis and resistance to a variety of apoptotic stimuli.
