A novel receptor for Apo2L/TRAIL contains a truncated death domain

Apo2 ligand (Apo2L [1], also called TRAIL for tumor necrosis factor (TNF)-related apoptosis-inducing ligand [2]) belongs to the TNF family and activates apoptosis in tumor cells, Three closely related receptors bind Apo2L: DR4 and DR5, which contain cytoplasmic death domains and signal apoptosis, and DcR1, a decoy receptor that lacks a cytoplasmic tail and inhibits Apo2L function [3-5], By cross hybridization with DcR1,we have identified a fourth Apo2L receptor, which contains a cytoplasmic region with a truncated death domain, We subsequently named this protein decoy receptor 2 (DcR2), The DcR2 gene mapped to human chromosome 8p21, as did the genes encoding DR4, DR5 and DcR1,A single DcR2 mRNA transcript showed a unique expression pattern in human tissues and was particularly abundant in fetal liver and adult testis, Upon overexpression, DcR2 did not activate apoptosis or nuclear factor-kappa B; however, it substantially reduced cellular sensitivity to Apo2L-induced apoptosis, These results suggest that DcR2 functions as an inhibitory Apo2L receptor.