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-kappaB; however, it substantially reduced cellular sensitivity to Apo2L-induced apoptosis. These results suggest that DcR2 functions as an inhibitory Apo2L receptor.
Marsters
S A
SA
Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080-4918, USA.
Sheridan
J P
JP
Pitti
R M
RM
Huang
A
A
Skubatch
M
M
Baldwin
D
D
Yuan
J
J
Gurney
A
A
Goddard
A D
AD
Godowski
P
P
Ashkenazi
A
A
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
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