title: A novel receptor for Apo2L/TRAIL contains a truncated death domain.
abstract: 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.
authors.affiliation: Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080-4918, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Marsters
authors.forename: J P
authors.initials: JP
authors.lastname: Sheridan
authors.forename: R M
authors.initials: RM
authors.lastname: Pitti
authors.forename: A
authors.initials: A
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Skubatch
authors.forename: D
authors.initials: D
authors.lastname: Baldwin
authors.forename: J
authors.initials: J
authors.lastname: Yuan
authors.forename: A
authors.initials: A
authors.lastname: Gurney
authors.forename: A D
authors.initials: AD
authors.lastname: Goddard
authors.forename: P
authors.initials: P
authors.lastname: Godowski
authors.forename: A
authors.initials: A
authors.lastname: Ashkenazi
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002461:Cell Line, Transformed; D002898:Chromosomes, Human, Pair 8; D018076:DNA, Complementary; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor