The two decoy receptors compete for TRAIL binding with the death receptors at similar binding affinities., Additionally, TRAIL binds the soluble receptor osteoprotegerin that negatively regulates osteoclastogenesis and bone resorption, though the interaction is much weaker than that of the other TRAIL receptors.
Caspase-8 facilitates cell death initiated from the death receptor pathway after a death ligand (e.g., TRAIL) binds a death receptor (e.g., DR5) [48].
Taken together, these results confirm direct binding of UL141 to both human TRAIL DRs, but with significantly lower affinity for TRAIL-R1, largely mimicking how TRAIL binds its two cognate DRs (Truneh et al., 2000).
When TRAIL binds the receptors R1 and R2, the death signal is transmitted through their intracellular protein protein interacting death domains via cytoplasmic adaptor molecules resulting in an early activation of caspase-8 (Griffith et al, 1998; MacFarlane et al, 2000a).
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to its receptors, TRAIL-receptor 1 (TRAIL-R1) and TRAIL-receptor 2 (TRAIL-R2), leading to apoptosis by activation of caspase-8 and the downstream executioner caspases, caspase-3 and caspase-7 (caspase-3/7).
TRAIL signaling provides another level of complexity compared with CD95L signaling because TRAIL binds to two death receptors TRAIL-R1 and TRAIL-R2 as well as to several decoy receptors.
When TRAIL binds to DR4 and/or DR5 receptors, the death receptors become trimerized and then recruit the adaptor protein FADD (Fas-associated protein with death domain) and procaspase 8 or procaspase 10 to form the DISC, leading to caspase 8 activation [1], [2].
The ligand TRAIL binds to five receptors.
For signaling, TRAIL binds to five target proteins, namely TRAIL-R1 4 TRAIL-R1 4rotegerin.
TRAIL binds also to three decoy receptors, DcR1, DcR2 and OPG.
