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

Mariapia A. Degli-Esposti, William C. Dougall, Pamela J. Smolak, Jennifer Y. Waugh, Craig A. Smith, Raymond G. Goodwin

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735 Citations (Scopus)


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-κB 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.

Original languageEnglish
Pages (from-to)813-820
Number of pages8
Issue number6
Publication statusPublished - 1 Jan 1997
Externally publishedYes

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