The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain

Immunity. 1997 Dec;7(6):813-20. doi: 10.1016/s1074-7613(00)80399-4.


A fourth member of the emerging TRAIL receptor family, TRAIL-R4, has been cloned and characterized. TRAIL-R4 encodes a 386-amino acid protein with an extracellular domain showing 58%-70% identity to those of TRAIL-R1, TRAIL-R2, and TRAIL-R3. The signaling capacity of TRAIL-R4 is similar to that of TRAIL-R1 and TRAIL-R2 with respect to NF-kappaB activation, but differs in its inability to induce apoptosis. Yet TRAIL-R4 retains a C-terminal element containing one third of a consensus death domain motif. Transient overexpression of TRAIL-R4 in cells normally sensitive to TRAIL-mediated killing confers complete protection, suggesting that one function of TRAIL-R4 may be inhibition of TRAIL cytotoxicity. Like TRAIL-R1 and TRAIL-R2, this receptor shows widespread tissue expression. The human TRAIL-R4 gene has been mapped to chromosome 8p22-21, clustered with three other TRAIL receptors.

MeSH terms

  • Amino Acid Sequence
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Base Sequence
  • Binding Sites
  • DNA, Complementary
  • Humans
  • Jurkat Cells
  • Membrane Glycoproteins / metabolism*
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Sequence Homology, Amino Acid
  • TNF-Related Apoptosis-Inducing Ligand
  • Tissue Distribution
  • Tumor Necrosis Factor-alpha / metabolism*


  • Apoptosis Regulatory Proteins
  • DNA, Complementary
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha

Associated data

  • GENBANK/AF021232
  • GENBANK/AF021233