TWEAK, a New Secreted Ligand in the Tumor Necrosis Factor Family That Weakly Induces Apoptosis

• Published in: The Journal of biological chemistry Vol. 272; no. 51; pp. 32401 - 32410
• Main Authors: Chicheportiche, Yves, Bourdon, Paul R., Xu, Haoda, Hsu, Yen-Ming, Scott, Hamish, Hession, Catherine, Garcia, Irene, Browning, Jeffrey L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-12-1997; American Society for Biochemistry and Molecular Biology
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Amino Acid Sequence; Animals; Apoptosis; Apoptosis Regulatory Proteins; Base Sequence; Blotting, Northern; Carrier Proteins - genetics; Carrier Proteins - metabolism; Chemokines - metabolism; Chromosome Mapping; Chromosomes, Human, Pair 17; Cytokine TWEAK; DNA, Complementary; Humans; Ligands; Mice; Molecular Sequence Data; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Signal Transduction; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.51.32401

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.