title: Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
abstract: Tumor necrosis factor (TNF) ligand and receptor superfamily members play critical roles in diverse developmental and pathological settings. In search for novel TNF superfamily members, we identified a murine chromosomal locus that contains three new TNF receptor-related genes. Sequence alignments suggest that the ligand binding regions of these murine TNF receptor homologues, mTNFRH1, -2 and -3, are most homologous to those of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors. By using a number of in vitro ligand-receptor binding assays, we demonstrate that mTNFRH1 and -2, but not mTNFRH3, bind murine TRAIL, suggesting that they are indeed TRAIL receptors. This notion is further supported by our demonstration that both mTNFRH1:Fc and mTNFRH2:Fc fusion proteins inhibited mTRAIL-induced apoptosis of Jurkat cells. Unlike the only other known murine TRAIL receptor mTRAILR2, however, neither mTNFRH2 nor mTNFRH3 has a cytoplasmic region containing the well characterized death domain motif. Coupled with our observation that overexpression of mTNFRH1 and -2 in 293T cells neither induces apoptosis nor triggers NFkappaB activation, we propose that the mTnfrh1 and mTnfrh2 genes encode the first described murine decoy receptors for TRAIL, and we renamed them mDcTrailr1 and -r2, respectively. Interestingly, the overall sequence structures of mDcTRAILR1 and -R2 are quite distinct from those of the known human decoy TRAIL receptors, suggesting that the presence of TRAIL decoy receptors represents a more recent evolutionary event.
authors.affiliation: Department of Exploratory Sciences, Biogen, Inc., Cambridge, Massachusetts 02142, USA.
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.forename: Dian
authors.initials: D
authors.lastname: Olson
authors.forename: Aubry
authors.initials: A
authors.lastname: Tardivel
authors.forename: Beth
authors.initials: B
authors.lastname: Browning
authors.forename: Alexey
authors.initials: A
authors.lastname: Lugovskoy
authors.forename: DaHai
authors.initials: D
authors.lastname: Gong
authors.forename: Max
authors.initials: M
authors.lastname: Dobles
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hertig
authors.forename: Kay
authors.initials: K
authors.lastname: Hofmann
authors.forename: Herman
authors.initials: H
authors.lastname: Van Vlijmen
authors.forename: Yen-Ming
authors.initials: YM
authors.lastname: Hsu
authors.forename: Linda C
authors.initials: LC
authors.lastname: Burkly
authors.forename: Jurg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Zheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D002874:Chromosome Mapping; D019143:Evolution, Molecular; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D017421:Sequence Analysis; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha