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

The Tumor necrosis factor receptor superfamily member 6, commonly known as the Fas receptor or CD95, is a critical cell surface receptor that initiates the extrinsic apoptotic pathway upon binding to its ligand, FasL. This interaction leads to the formation of the death-inducing signaling complex (DISC), which activates procaspase-8 and subsequently triggers a proteolytic cascade resulting in cell death [StatPearls, Physiology, Apoptosis, 2023]. Fas is highly expressed on activated T cells and is essential for maintaining immune homeostasis by eliminating self-reactive lymphocytes and terminating immune responses through a process known as activation-induced cell death [UniProt, P25445]. In oncology, many tumors downregulate Fas or express dominant-negative mutants to evade immune surveillance, making the restoration of Fas signaling a therapeutic goal [PubMed, PMC2649354]. However, the clinical application of Fas agonists has been severely limited by systemic toxicity, particularly lethal hepatotoxicity, due to the high sensitivity of hepatocytes to Fas-mediated apoptosis [PubMed, 10.1038/sj.cdd.4400975]. Conversely, Fas antagonists like Asunercept are being investigated to prevent pathological cell death in conditions such as graft-versus-host disease and myelodysplastic syndromes [ClinicalTrials.gov, NCT00879151].

Other names

CD95APO-1TNFRSF6Apoptosis-mediating surface antigen FASAPT1FAS1

Agonism to induce extrinsic apoptosis in target cells (e.g., cancer cells); Antagonism to prevent Fas-mediated cell death in inflammatory or autoimmune conditions (e.g., blocking FasL binding).