Background
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.
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