Apoptosis mediated by death factors like FasL and TNF-α involves the formation of a death-inducing signaling complex to their respective receptors. Upon ligand activation to their receptors, Fas and TNF-R1 associate with death domain containing adaptor proteins FADD and TRADD. In addition to its carboxy-terminal DD, FADD contains an amino-terminal death effector domain that binds to DEDs found on caspase-8 which leads to activation of this initiator caspase. Caspase-8 subsequently activates downstream effector caspases, like caspase-3, resulting in the cleavage of proteins involved in the execution of apoptosis. Unlike FADD, TRADD does not contain a DED. Apoptosis driven by TNF-R1 binding to TRADD involves association of TRADD and FADD which then leads to activation of caspase-8.
[1] Nagata, S. (1997) Cell 88, 355-65.
[2] Chinnaiyan, A.M. et al. (1995) Cell 81, 505-12.
[3] Boldin, M.P. et al. (1995) J. Biol. Chem. 270, 7795-8.
[4] Hsu, H. et al. (1995) Cell 81, 495-504.
[5] Muzio, M. et al. (1996) Cell 85, 817-27.
[6] Boldin, M.P. et al. (1996) Cell 85, 803-15.
[7] Hsu, H. et al. (1996) Cell 84, 299-308.
