Nonapoptotic functions of FADD-binding death receptors and their signaling molecules

Death receptors (DRs) are surface receptors that when triggered have the capacity to induce apoptosis in cells by forming the death-inducing signaling complex (DISC). The first protein recruited to form the DISC is the adaptor protein FADD/Mort1. Some members of the DR family, CD95 and the TRAIL receptors DR4 and DR5, directly bind FADD, whereas others, such as TNF receptor I and DR3, initially bind another adaptor protein, TRADD, which then recruits FADD. While all DRs can activate both apoptotic and non-apoptotic pathways, it has been widely assumed that the main physiological role of FADD-binding death receptors is to trigger apoptosis. However, recent work has ascribed multiple non-apoptotic activities to these receptors and/or the signaling components of the DISC.