TRAIL ELISA Kit, Human

The interaction of TRAIL with its two death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) is the initial step in TRAIL-induced apoptosis. The binding of TRAIL leads to trimerization of the death receptors and activation of receptor-mediated death pathway. The activated death receptors recruit and activate an adaptor protein called Fas-associated death domain (FADD) through interactions between the death domain (DD) on the death receptors and FADD. The death effector domain (DED) of FADD recruits and activates caspase-8, leading to the formation of the death-inducing signaling complex (DISC). In type I cells, the presence of activated caspase-8, is sufficient to induce activation of one or more effector caspases (e.g., caspase-3 or -7), which then act on final death substrates in apoptosis. However, in type II cells, even a small amount of activated caspase-8, although not enough to activate the effector caspases, is sufficient to trigger a mitochondria-dependent apoptotic amplification loop by activating Bid, which induces the accumulation of Bax in mitochondria, the release of cytochrome c from mitochondria, the activation of caspase-9, caspase-3, and caspase-7, and finally, programmed cell death.² In addition to inducing apoptosis by caspase-8 recruitment through FADD, TRAIL binding to its receptors also leads to activation of the transcription factor nuclear factor-kappa B (NF-kB). TRAIL death receptors, like the TNF receptor 1 (TNFR1), activate NF- NF-kB through the TNFR1-associated death domain protein (TRADD). Activated TRADD recruits the DD-containing protein RIP and TNF receptor-associated factor-2 (TRAF2), leading to activation of the NF-kB pathway; in contrast, dominant-negative TRADD can block the NF-kB activation induced by TRAIL receptors. In TNFR1 signaling, TRADD is believed to be upstream of FADD. However, in TRAIL signaling, TRADD may be mediated by FADD, because TRADD recruitment to the DISC is observed only in the presence of FADD.³