TNF-related apoptosis-inducing ligand (TRAIL)

TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein and a cytokine belonging to the tumor necrosis factor (TNF) superfamily[1][2][4]. TRAIL is produced as a homotrimer and can exist in both membrane-bound and soluble forms, the latter generated by proteolytic cleavage from the cell surface[2][3][4]. TRAIL primarily functions by binding to death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) on target cells, inducing apoptosis predominantly in cancer cells while sparing most normal cells, via formation of the death-inducing signaling complex (DISC) and activation of caspase-dependent pathways[1][3][7][9]. TRAIL also interacts with decoy receptors (DcR1, DcR2) and osteoprotegerin, which modulate its activity and can prevent inappropriate apoptosis[1][5]. TRAIL plays crucial roles in tumor immune surveillance and the regulation of apoptosis, making it a therapeutically important target for cancer therapy, especially for agents aiming to restore or enhance TRAIL-induced apoptotic pathways in resistant tumors[3][4][7]. Resistance and poor pharmacokinetics are key therapeutic challenges[4].

Other names

Apo2 ligandApo2LCD253TNFSF10tumor necrosis factor ligand superfamily member 10

Induction of apoptosis by binding to death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2), resulting in receptor trimerization, formation of the death-inducing signaling complex (DISC), recruitment of FADD (Fas-associated death domain), and activation of caspase-8 and downstream effector caspases[1][3][7][9]. Selective cytotoxicity for tumor cells, sparing most normal cells[1][3][7].