Cells undergo programmed cell death (Apoptosis) in response to various stimuli. Apoptosis is essential for morphogenesis, tissue homeostasis, and host defense. Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors, TNFR1 and Fas. A novel death domain containing receptors have been recently identified and designated DR4 and DR5 (for death receptor 4). DR4 and DR5 are functional receptors for TRAIL, and DcR1/TRID and DcR2 are decoy receptors1-3. DcR1 is also designated as TRAIL-R3, TRID or LIT2-7. DcR1 has an extracellular TRAIL-binding domain but lacks intracellular death domain and does not induce apoptosis. TRAIL-R3 also has several sites for potential N- (5 sites) and O-linked (approximately 20) glycosylation and GPI addition. Antibodies made against TRAIL-R3/DcR1 detects a protein of approximate molecular mass of 65kDa in the western blot analysis under denaturing and reducing conditions instead of theoretical Mr of 29 kDa6. The slow migration of this protein in SDS-PAGE is probably due to the presence of 5 TAPE (threonine, alanine, proline, and glutamine-rich) repeats. The TAPE repeat-deficient receptor migrates normally in SDS-PAGE6. Unlike TRAIL-R1 (DR4) and TRAIL-R2 (DR5), DcR1/TRAIL-R3 transcript is restricted to skeletal muscle, peripheral blood lymphocytes, and the spleen.
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