Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL)

TRAIL is a recently identified member of the TNF gene superfamily. Five different receptors have been identified for TRAIL. Two receptors, DR4 and DR5, are transmembrane proteins containing death domain similar to FAS and other TNF family receptors. Two other receptors, DcR1 and DcR2, act like decoy proteins for TRAIL binding because they lack the death domain. TRAIL can also bind, though weakly, to osteoprotegrin (OPG), a soluble receptor, which plays a role in osteoclastogenesis. TRAIL induces apoptosis in various tumor cell lines, whereas most primary cells seem to be resistant. TRAIL-mediated apoptosis occurs following its binding to DR4 or DR5 receptors. The mechanism of apoptosis involves activation of caspase-8 and subsequent activation of effector caspases.