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

1997; Elsevier BV; Volume: 7; Issue: 12 Linguagem: Inglês

10.1016/s0960-9822(06)00422-2

1879-0445

Scot A. Marsters, James P. Sheridan, Robert Pitti, Arthur Huang, Maya Skubatch, Daryl T. Baldwin, Jianwei Yuan, Austin Gurney, Audrey D. Goddard, Paul J. Godowski, Avi Ashkenazi,

NF-κB Signaling Pathways

Apo2 ligand (Apo2L [[1]Pitti RM Marsters SA Ruppert S Donahue CJ Moore A Ashkenazi A Induction of apoptosis by Apo-2 Ligand, a new member of the tumor necrosis factor receptor family.J Biol Chem. 1996; 271: 12697Google Scholar], also called TRAIL for tumor necrosis factor (TNF)-related apoptosis-inducing ligand [[2]Wiley SR Schooley K Smolak PJ Din WS Huang CP Nicholl JK et al.Identification and characterization of a new member of the TNF family that induces apoptosis.Immunity. 1995; 3 (96111955): 673-682Abstract Full Text PDF PubMed Scopus (2564) Google Scholar]) 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 [3Pan G O’Rourke K Chinnaiyan AM Gentz R Ebner R Ni J et al.The receptor for the cytotoxic ligand TRAIL.Science. 1997; 276 (97238921): 111-113Crossref PubMed Scopus (1489) Google Scholar, 4Sheridan JP Marsters SA Pitti RM Gurney A Skubatch M Baldwin D et al.Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors.Science. 1997; 277 (97390509): 818-821Crossref PubMed Scopus (1473) Google Scholar, 5Pan G Dixit VM An antagonist decoy receptor and a new death domain-containing receptor for TRAIL.Science. 1997; 277 (97390508): 815-818Crossref PubMed Scopus (1328) Google Scholar]. 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-κB; however, it substantially reduced cellular sensitivity to Apo2L-induced apoptosis. These results suggest that DcR2 functions as an inhibitory Apo2L receptor.