AN ANTAGONIST DECOY RECEPTOR AND A DEATH DOMAIN-CONTAINING RECEPTOR FOR TRAIL

TRAIL, also called Apo2L, is a cytotoxic protein that induces apoptosi s of many transformed cell fines but not of normal tissues, even thoug h its death domain-containing receptor, DR4, is expressed on both cell types. An antagonist decoy receptor (designated as TRID for TRAIL rec eptor without an intracellular domain) that may explain the resistant phenotype of normal tissues was identified. TRID is a distinct gene pr oduct with an extracellular TRAIL-binding domain and a transmembrane d omain but no intracellular signaling domain. TRID transcripts were det ected in many normal human tissues but not in most cancer cell lines e xamined. Ectopic expression of TRID protected mammalian cells from TRA IL-induced apoptosis, which is consistent with a protective role. Anot her death domain-containing receptor for TRAIL (designated as death re ceptor-5), which preferentially engaged a FLICE (caspase-8)-related de ath protease, was also identified.