The roles of FADD in extrinsic apoptosis and necroptosis

Fas-associated protein with death domain (FADD), an adaptorthat bridges death receptor signaling to the caspase cascade, isindispensible for the induction of extrinsic apoptotic cell death.Interest in the non-apoptotic function of FADD has greatlyincreased due to evidence that FADD-deficient mice ordominant-negative FADD transgenic mice result in embryoniclethality and an immune defect without showing apoptoticfeatures. Numerous studies have suggested that FADD regulatescell cycle progression, proliferation, and autophagy, affectingthese phenomena. Recently, programmed necrosis, also callednecroptosis, was shown to be a key mechanism that inducesembryonic lethality and an immune defect. Supporting thesefindings, FADD was shown to be involved in various necroptosismodels. In this review, we summarize the mechanism ofextrinsic apoptosis and necroptosis, and discuss the in vivo andin vitro roles of FADD in necroptosis induced by various stimuli.