CDB15:0001492 TNFSF10 — TNFRSF10A
Experimentally validated in Human; Orthology-inferred in Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
The receptor for the cytotoxic ligand TRAIL.
Science, 1997; PubMed, Homo sapiens TNFSF10 — Homo sapiens TNFRSF10A
ABSTRACT: TRAIL (also known as Apo-2L) is a member of the tumor necrosis factor (TNF) ligand family that rapidly induces apoptosis in a variety of transformed cell lines. The human receptor for TRAIL was found to be an undescribed member of the TNF-receptor family (designated death receptor-4, DR4) that contains a cytoplasmic "death domain" capable of engaging the cell suicide apparatus but not the nuclear factor kappa B pathway in the system studied. Unlike Fas, TNFR-1, and DR3, DR4 could not use FADD to transmit the death signal, suggesting the use of distinct proximal signaling machinery. Thus, the DR4-TRAIL axis defines another receptor-ligand pair involved in regulating cell suicide and tissue homeostasis.
Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL.
The Journal of biological chemistry, 1997; PubMed, Homo sapiens TNFSF10 — Homo sapiens TNFRSF10A
ABSTRACT: A human receptor for the cytotoxic ligand TRAIL (TRAIL receptor-1, designated DR4) was identified recently as a member of the tumor necrosis factor receptor family. In this report we describe the identification of two additional human TRAIL receptors, TRAIL receptor-2 and TRAIL receptor-3, that belong to the tumor necrosis factor receptor family. Interestingly, TRAIL receptor-2 but not TRAIL receptor-3 contains a cytoplasmic "death domain" necessary for induction of apoptosis and is hence designated death receptor-5 (DR5). Like DR4, DR5 engages the apoptotic pathway independent of the adaptor molecule FADD/MORT1. Because of its lack of a death domain, TRAIL receptor-3 is not capable of inducing apoptosis. However, by competing for TRAIL, it is capable of inhibiting TRAIL-induced apoptosis. Thus, TRAIL receptor-3 may function as an antagonistic decoy receptor to attenuate the cytotoxic effect of TRAIL in most tissues that are TRAIL+, DR4+, and DR5+.