TNF-related apoptosis-inducing ligand signaling complex (TRAIL signaling complex)

The TRAIL signaling complex, primarily known as the Death-Inducing Signaling Complex (DISC), is a multi-protein assembly that initiates the extrinsic apoptotic pathway upon the binding of TNF-related apoptosis-inducing ligand (TRAIL/TNFSF10) to its agonist receptors, Death Receptor 4 (DR4/TNFRSF10A) and Death Receptor 5 (DR5/TNFRSF10B) [2, 15, 43]. Ligand binding induces receptor trimerization and the recruitment of the adaptor protein FADD, which subsequently recruits and activates initiator pro-caspases 8 and 10 [11, 15, 32]. This activation triggers a downstream proteolytic cascade of effector caspases, leading to programmed cell death [11, 27, 43]. The TRAIL system is highly valued in oncology due to its ability to selectively induce apoptosis in malignant cells while sparing most normal tissues [2, 11, 27]. Beyond apoptosis, the complex can also activate non-canonical pathways such as NF-κB and MAPK, which may promote cell survival or inflammation depending on the cellular context and the presence of inhibitors like c-FLIP [2, 11, 46]. Note: The term "DR3" (Death Receptor 3/TNFRSF25) refers to a distinct receptor that binds the ligand TL1A rather than TRAIL, although it shares similar signaling motifs and can also form a DISC-like complex [1, 13, 44].

Other names

TRAIL-R1/R2 signaling complexApo2L signaling complexTRAIL DISCDeath-inducing signaling complex (DISC)TRAIL-R1/R2-FADD-Caspase-8 complex

Death receptor agonism, Caspase-8/10 activation, Apoptosis induction, TL1A neutralization (for DR3-related components)