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The receptor for the cytotoxic ligand TRAIL
G Pan1, K O'Rourke, A M Chinnaiyan
1Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Science (New York, N.Y.)
|April 4, 1997
Summary
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis via a novel receptor, death receptor-4 (DR4). This DR4-TRAIL pathway regulates cell suicide and tissue homeostasis, distinct from other known death receptors.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- TRAIL (TNF-related apoptosis-inducing ligand), also known as Apo-2L, is a TNF ligand family member.
- TRAIL induces apoptosis in various transformed cell lines.
Purpose of the Study:
- Identify the human receptor for TRAIL.
- Characterize the signaling mechanism of the TRAIL-receptor interaction.
Main Methods:
- Receptor identification and characterization.
- Analysis of signaling pathways involved in apoptosis induction.
Main Results:
- The human TRAIL receptor was identified as a novel TNF-receptor family member, designated death receptor-4 (DR4).
- DR4 possesses a cytoplasmic death domain that activates the cell suicide apparatus.
- DR4 signaling for apoptosis does not involve FADD, unlike Fas, TNFR-1, and DR3, suggesting a distinct proximal signaling mechanism.
Conclusions:
- The DR4-TRAIL axis represents a new receptor-ligand pair crucial for regulating apoptosis.
- This pathway plays a role in maintaining tissue homeostasis.
- DR4 utilizes a unique signaling pathway independent of FADD for apoptosis induction.