Tumor necrosis factor receptor superfamily member 10A (TRAIL-R1) and Tumor necrosis factor receptor superfamily member 10B (TRAIL-R2) (TRAIL-R1/R2)

Tumor necrosis factor receptor superfamily member 10A (TRAIL-R1/DR4) and member 10B (TRAIL-R2/DR5) are transmembrane proteins that function as the primary death receptors for the TRAIL ligand (UniProt P50591, O14763). Upon ligand binding, these receptors undergo trimerization and recruit the adapter protein FADD and pro-caspase 8 to form the Death-Inducing Signaling Complex (DISC), which triggers the extrinsic apoptosis pathway (PubMed: 29904001). These receptors are highly relevant in oncology because they are often overexpressed in cancer cells compared to normal tissues, providing a mechanism for selective tumor cell destruction (PubMed: 25365252). Therapeutic development has focused on recombinant TRAIL variants and agonistic monoclonal antibodies to activate these receptors directly (PubMed: 30610226). Although early clinical trials faced challenges such as low potency and resistance, newer multivalent agonists and combination strategies are being developed to enhance therapeutic efficacy (PubMed: 33432167).

Other names

Death receptor 4Death receptor 5DR4DR5TNFRSF10ATNFRSF10BAPO2CD261CD262TRAIL-RTR1TR2Tumor necrosis factor receptor superfamily member 10ATumor necrosis factor receptor superfamily member 10B

Agonism of TRAIL-R1 and TRAIL-R2 induces receptor trimerization and the formation of the Death-Inducing Signaling Complex (DISC), leading to the activation of Caspase-8 and Caspase-10 and the subsequent execution of the extrinsic apoptotic pathway (PubMed: 29904001).