Figure 2.

TRAIL-induced apoptotic pathways. After trimerization, TRAIL binds to death receptors, which triggers the formation of the DISC and activates caspase-8/10. Subsequently, activated caspase-8/10 induces cleavage of caspase-3/7, which leads to apoptosis. On the other hand, cleaved caspase-8/10 can also recruit Bid to trigger apoptosis via the intrinsic pathways. The intrinsic pathway is usually activated by DNA damage followed by p53 activation, whereas TRAIL-induced intrinsic apoptotic pathway is independent of p53. Interestingly, p53 has also been found to regulate TRAIL receptors DR4, DR5, DcR1, and DcR2^[104-107]. Anti-apoptotic proteins, including c-FLIP, c-IAP1/2, Bcl-2, Bfl-1, Mcl-1, Bcl-X_L, XIAP, and survivin, are shown in blue circles. DISC: death-inducing signalling complex; DR4: death receptor 4; DR4: death receptor 5; DcR1: decoy receptor 1; DcR2: decoy receptor 2