Journal of Biological Chemistry
Volume 272, Issue 51, 19 December 1997, Pages 32401-32410
Journal home page for Journal of Biological Chemistry

CELL BIOLOGY AND METABOLISM
TWEAK, a New Secreted Ligand in the Tumor Necrosis Factor Family That Weakly Induces Apoptosis*

https://doi.org/10.1074/jbc.272.51.32401Get rights and content
Under a Creative Commons license
open access

The members of the tumor necrosis factor (TNF) family play pivotal roles in the regulation of the immune system. Here we describe a new ligand in this family, designated TWEAK. The mouse and human versions of this protein are unusually conserved with 93% amino acid identity in the receptor binding domain. The protein was efficiently secreted from cells indicating that, like TNF, TWEAK may have the long range effects of a secreted cytokine. TWEAK transcripts were abundant and found in many tissues, suggesting that TWEAK and TRAIL belong to a new group of widely expressed ligands. Like many members of the TNF family, TWEAK was able to induce interleukin-8 synthesis in a number of cell lines. The human adenocarcinoma cell line, HT29, underwent apoptosis in the presence of both TWEAK and interferon-γ. Thus, TWEAK resembles many other TNF ligands in the capacity to induce cell death; however, the fact that TWEAK-sensitive cells are relatively rare suggests that TWEAK along with lymphotoxins α/β and possibly CD30L trigger death via a weaker, nondeath domain-dependent mechanism.

Cited by (0)

*

This work was supported in part by Grants 31-42275.94 and 32-41729.94 (to I. G.) from the Swiss National Fund.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF030099 and AF030100.