Multifunctional Role of Fas-Associated Death Domain Protein in Apoptosis

The Fas-associated death domain protein (FADD) wasdiscovered as a protein that interacts with the Fas receptor(Chinnaiyan et al., 1995; Zhang and Winoto, 1996). FADDconsists of two distinct domains called the ‘death effectordomain’ and the ‘death domain’ at its N- and C-terminus,respectively. The death domain of FADD (FADD-DD)interacts with the death domain of the Fas receptor, and thedeath effector domain of FADD (FADD-DED) interacts withthe death effector domain of procaspase-8 (Boldin et al.,1996; Muzio et al., 1996). In Fas-mediated apoptosis, FADDis recruited to the Fas receptor, and recruits procaspase-8 inturn. This results in the initiation of apoptotic processes(Medema et al., 1997; Muzio et al., 1998). However, FADD isalso involved in T-cell proliferation (Zhang et al., 1998; Walshet al., 1998 ) and necrosis (Kawahara et al., 1998; Matsumuraet al., 2000), independent of known apoptosis mechanisms. Inthis article, the suggested roles of FADD in various pathwayswill be reviewed.