Tumor necrosis factor receptor superfamily member 6 (FAS) (FAS)

Tumor necrosis factor receptor superfamily member 6, commonly known as FAS or CD95, is a cell surface death receptor that plays a fundamental role in the extrinsic apoptosis pathway. Upon binding to its ligand (FASL), the receptor clusters to form a death-inducing signaling complex (DISC), which activates the caspase cascade to execute programmed cell death. This process is vital for immune homeostasis, particularly in the deletion of autoreactive lymphocytes and the termination of immune responses. In clinical contexts, mutations in the FAS gene can lead to Autoimmune Lymphoproliferative Syndrome (ALPS), while its downregulation is a frequent mechanism for immune escape in various cancers. Although FAS agonists were early candidates for cancer therapy, their development has been severely limited by life-threatening hepatotoxicity. Current therapeutic efforts focus on using soluble decoy receptors like Asunercept to block excessive FAS-mediated cell death in conditions such as glioblastoma and myelodysplastic syndromes, or engineering bispecific antibodies to localize FAS activation specifically to tumor cells.

Other names

CD95APO-1Apoptosis antigen 1APT1TNFRSF6Fas receptorFAS1FASTM

FAS ligand binding to the FAS receptor induces receptor trimerization and the assembly of the death-inducing signaling complex (DISC). This complex recruits FADD (Fas-associated death domain) and procaspase-8, leading to the activation of executioner caspases (caspase-3, -6, and -7) and subsequent cell death. Therapeutic inhibitors like Asunercept act as decoy receptors to bind FAS ligand (FASL) and prevent this signaling cascade in conditions of pathological cell death.