In contrast to growth factors which promote cell proliferation, FAS ligand (FAS-L) and the tumor necrosis factors (TNFs) rapidly induce apoptosis. Cellular response to FAS-L and TNF is mediated by structurally related receptors containing a conserved 'death domain' and belonging to the TNF receptor superfamily. TRADD, FADD and RIP are FAS/TNF-RI interacting proteins that contain a death domain homologous region (DDH). TRADD (TNF-RI-associated death domain) and FADD (FAS-associated death domain) associate with the death domains of both FAS and TNF-RI via their DDH regions, while RIP associates exclusively with FAS. An additional FAS interacting protein designated FAF1, for FAS-associated protein factor-1, binds with the cytoplasmic tail of wildtype but not LPR mutant FAS. When overexpressed in cells, FAF1 enhances the efficiency of FAS-mediated apoptosis. In contrast to TRADD, FADD and RIP, FAF1 lacks a DDH and cannot induce apoptosis independently of FAS activation.