Tumor necrosis factor receptor superfamily member 6 is a protein in humans that is encoded by FAS gene. Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro).
FAS, also known as CD95/Apo-1/TNFRSF6, is a type I transmembrane (TM) protein on the cell surface, and a death receptor that belongs to the TNF-receptor superfamily. Fas contains an N-terminal ligand-binding extracellular domain (ECD), a TM domain, and a C-terminal cytoplasmic death domain (DD). Expressed at the cell surface as a homotrimer, the FAS receptor implements both apoptotic and non-apoptotic signaling pathways. The ligation of FAS with FAS ligand (FASL) leads to the activation of a caspase cascade that initiates apoptosis. FAS triggers apoptosis through FADD-mediated recruitment and activation of caspase-8. Fas–FasL-induced apoptosis is an important mechanism for the maintenance of immune homeostasis ＆peripheral tolerance, and the surveillance of tumor. Its non-apoptotic cues seem to promote oncogenesis. FAS/CD95 engagement also induces non-apoptotic signaling pathways promoting cell motility, invasiveness, inflammation, and organ regeneration. A large fraction of human ALPS (autoimmune lymphoproliferative syndrome) patients have heterozygous inherited mutations in the FAS gene. ALPS is an inherited disorder in which the body cannot properly regulate the number of immune system cells (lymphocytes). In consideration of the multiple roles of Fas–FasL in immune responses and diseases, therapeutic targets of the Fas/FasL pathway might not protect against a specific disease rather than influencing the patient's prognosis.