Fas receptor (also known as CD95 or apoptosis antigen 1) and Fas ligand (Fas (for Fas receptor), FasL (for Fas ligand))

The Fas receptor (CD95, APO-1, TNFRSF6) is a type I transmembrane death receptor and member of the tumor necrosis factor (TNF) receptor superfamily, containing a cysteine-rich extracellular domain and a cytoplasmic 'death domain'[1][2][3][4]. Fas interacts with Fas ligand (FasL), a TNF family member, to form the death-inducing signaling complex (DISC), recruiting FADD and activating caspase-8, resulting in apoptosis[1][2][3][4]. While membrane-bound FasL induces Fas clustering and signaling, some experimental therapies and intracellular pathways can trigger Fas receptor activation independently of FasL, often enhanced by membrane lipid signaling[1]. Fas/FasL signaling plays essential roles in immune system regulation, especially in negative selection of lymphocytes, prevention of autoimmune disease, and tissue homeostasis. Genetic defects in Fas or FasL lead to immune dysregulation and autoimmune disease. Pharmacologic agonism of Fas has been limited by unacceptable toxicity; conversely, tumor cells may downregulate Fas to escape apoptosis, making it a key cancer research target.

Other names

FasFas receptorCD95APO-1TNFRSF6 (Tumor necrosis factor receptor superfamily member 6)Apoptosis antigen 1APTFasL (for Fas ligand)FASLG (Fas ligand gene/protein)

Induction of apoptosis via death receptor pathway (ligand binding leads to receptor oligomerization, recruitment of FADD and caspase-8 activation); Formation of the death-inducing signaling complex (DISC); Some drugs and conditions induce ligand-independent activation (e.g., via membrane rafts or lipid mediators like ceramide); Direct antibody cross-linking (experimental); Ceramide-mediated signal amplification