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

• Published in: Current biology 1997-12, Vol.7 (12), p.1003-1006
• Main Authors: Marsters, S A, Sheridan, J P, Pitti, R M, Huang, A, Skubatch, M, Baldwin, D, Yuan, J, Gurney, A, Goddard, A D, Godowski, P, Ashkenazi, A
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Sequence; Apoptosis; Apoptosis Regulatory Proteins; Base Sequence; Cell Line, Transformed; Chromosomes, Human, Pair 8; DNA, Complementary; fas Receptor - metabolism; HeLa Cells; Humans; Membrane Glycoproteins - metabolism; Molecular Sequence Data; Receptors, Tumor Necrosis Factor - chemistry; Receptors, Tumor Necrosis Factor - genetics; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Sequence Homology, Amino Acid; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0960-9822
• DOI: 10.1016/S0960-9822(06)00422-2

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-kappaB; however, it substantially reduced cellular sensitivity to Apo2L-induced apoptosis. These results suggest that DcR2 functions as an inhibitory Apo2L receptor.