The dark side of TRAIL signaling.

摘要

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF receptor ligand family that was discovered in the mid-nineties.12 The TRAIL system comprises four transmembrane TRAIL receptors, two of which are agonistic receptors that signal to cell death (i.e., TRAIL-R1, TRAIL-R2), while the other two are antagonistic receptors (i.e., TRAIL-R3, TRAIL-R4) that do not transmit a death signal and thus can confer resistance toward TRAIL-induced apoptosis.3 As TRAIL can bind to any of these four receptors, relative expression levels of TRAIL receptors on the cell's surface determine, at least in part, the outcome of the TRAIL response. Thus, based on this organization of the TRAIL receptors, there is already an inbuilt dichotomy in the TRAIL system, which has been implicated in the higher susceptibility of cancer versus normal non-malignant cells to TRAIL-induced cell death.