Molecular oncology. Causes of cancer and targets for treatment. Cambridge University Press (2014)
A subgroup of the TNF-receptor family called decoy receptors (DcR) can bind to extra-cellular death ligands, but are unable to transmit the death signal (Figure 30.5). Thus, decoy receptors, such as DcR1 (TRAIL-R3; 48–49), DcR2 (TRAIL-R4; 50), DcR3 (51), and osteoprotegerin (OPG) act as membrane-bound sinks for death-inducing ligands (52). Like DRs, DcRs have multiple CRDs at their N-terminus for ligand binding, but they lack all or part of the cytosolic DD that is required for DISC formation to signal cell death. DcR1, DcR2, and OPG are decoy receptors for the ligand TRAIL (53–54). DcR1 and DcR2 bind to TRAIL with high affinity and are strong inhibitors of TRAIL-induced apoptosis. DcR1 is attached to the plasma membrane through a glycophospholipid anchor and lacks the intra-cellular domain. DcR2 is a transmembrane protein with a truncated DD that does not interact with FADD or TRADD. OPG is a secreted, soluble protein that only binds to TRAIL with low affinity and is suggested to regulate osteoclastogenesis. DcR3 is a secreted protein and is the closest sequence homolog of OPG. DcR3 is the decoy receptor for FasL, LIGHT, and TL1A (54). In this manner, decoy death receptors modulate immune responses and protect tumor cells from host immune responses.
Figure 30.5. Caspase-8 stabilization. Caspase-8 can be polyubiquitinated by the E3 ubiquitin-ligase cullin3 (CUL3) to facilitate binding to ubiquitin-binding protein p62 at protected sites.