Fas receptor, TNF-related apoptosis-inducing ligand receptor (Fas, TRAIL (often refers to both the ligand and receptors; for the receptors, DR4/TRAIL-R1, DR5/TRAIL-R2))

The Fas receptor and TRAIL receptors (DR4/TRAIL-R1, DR5/TRAIL-R2) are members of the tumor necrosis factor receptor superfamily and function as death receptors. Upon binding their respective ligands (Fas ligand for Fas, TRAIL for DR4/DR5), these receptors trimerize and recruit the adaptor protein FADD, which in turn recruits procaspase-8 and -10 to form the DISC. This leads to caspase activation, initiating the extrinsic apoptotic pathway[1][2][6]. Fas signaling is critical for immune homeostasis, particularly in the deletion of activated lymphocytes, and defects in this pathway are linked to autoimmunity and lymphoproliferation[1][5]. TRAIL receptors are widely expressed in normal tissues but can selectively induce apoptosis in transformed cells, making them attractive cancer therapeutic targets; however, cancer cells often develop resistance through diverse mechanisms[2]. Both Fas and TRAIL receptors can also activate non-apoptotic pathways (e.g., NF-κB, ERK, Akt), which may contribute to tumor progression and immune evasion in certain contexts[2]. The structural basis for Fas receptor signaling involves a unique trimeric transmembrane domain assembly stabilized by a proline-containing motif, and similar principles may apply to other TNF receptor family members[1].

Other names

CD95Apo-1APT1TNFRSF6 (Tumor Necrosis Factor Receptor Superfamily Member 6)Fas cell surface death receptorDR4 (Death Receptor 4)TRAIL-R1TNFRSF10A (Tumor Necrosis Factor Receptor Superfamily Member 10A)DR5 (Death Receptor 5)TRAIL-R2TNFRSF10B (Tumor Necrosis Factor Receptor Superfamily Member 10B)

Induction of apoptosis via extrinsic pathway through formation of death-inducing signaling complex (DISC), leading to caspase-8/10 activation and downstream caspase cascade[1][2][6] - For TRAIL receptors, apoptotic signaling is similar to Fas, but can also activate non-apoptotic pathways (e.g., ERK, Akt, NF-κB) in certain contexts[2] - Mutations in Fas disrupt DISC formation, impairing apoptosis[1] - TRAIL signaling can be hijacked by tumors to promote survival, invasion, metastasis, and immune evasion[2]