An Antagonist Decoy Receptor and a Death Domain-Containing Receptor for TRAIL

TLDR

TRAIL is a cytotoxic protein that induces apoptosis in many transformed cell lines but not in normal tissues, a resistance that may be mediated by a decoy receptor lacking an intracellular domain and by a distinct death receptor, DR5. The study aimed to identify an antagonist decoy receptor, TRID, that could explain the resistance of normal tissues to TRAIL-induced apoptosis. TRID transcripts were found in many normal human tissues but not in most cancer cell lines, and ectopic expression of TRID protected mammalian cells from TRAIL-induced apoptosis, supporting a protective role.

Abstract

TRAIL, also called Apo2L, is a cytotoxic protein that induces apoptosis of many transformed cell lines but not of normal tissues, even though its death domain–containing receptor, DR4, is expressed on both cell types. An antagonist decoy receptor (designated as TRID for TRAIL receptor without an intracellular domain) that may explain the resistant phenotype of normal tissues was identified. TRID is a distinct gene product with an extracellular TRAIL-binding domain and a transmembrane domain but no intracellular signaling domain. TRID transcripts were detected in many normal human tissues but not in most cancer cell lines examined. Ectopic expression of TRID protected mammalian cells from TRAIL-induced apoptosis, which is consistent with a protective role. Another death domain–containing receptor for TRAIL (designated as death receptor–5), which preferentially engaged a FLICE (caspase-8)–related death protease, was also identified.