An Antagonist Decoy Receptor and a Death Domain-Containing Receptor for TRAIL
Guohua Pan,
*
Jian Ni,
*
Ying-Fei Wei,
*
Guo-liang Yu,
Reiner Gentz,
Vishva M. Dixit
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.
G. Pan and V. M. Dixit, Department of Pathology, University
of Michigan Medical School, Ann Arbor, MI, 48109, USA.
J. Ni, Y.-F. Wei, G.-L. Yu, R. Gentz, Human Genome Sciences, 9410 Key
West Avenue, Rockville, MD 20850-3338, USA.
*
These authors share first authorship.
To whom correspondence should be addressed at
Genentech, Inc., 1 DNA Way, M/S-40, So. San Francisco, CA 94080, USA. E-mail: dixit{at}gene.com
