A- DR4/DR5 receptor aggregation upon TRAIL treatment allows DISC formation, and caspase-8 processing. Cleaved caspase-8 can directly activate the effector caspases, or induce the mitochondrial amplification loop. (B) In presence of DcR1, TRAIL does not induce DISC formation, because of TRAIL titration in lipid rafts, whereas an anti-DR5 agonistic antibody allows DR5 aggregation and subsequent caspase-8 activation. (C) DcR2 interacts with DR5 and the processing of caspase-8 is inhibited. The anti-DR5 antibody induces cell death in DcR2 expressing cells.