title: TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis.
abstract: 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-gamma. 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 alpha/beta and possibly CD30L trigger death via a weaker, nondeath domain-dependent mechanism.
authors.affiliation: Department of Pathology, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Y
authors.initials: Y
authors.lastname: Chicheportiche
authors.forename: P R
authors.initials: PR
authors.lastname: Bourdon
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: Y M
authors.initials: YM
authors.lastname: Hsu
authors.forename: H
authors.initials: H
authors.lastname: Scott
authors.forename: C
authors.initials: C
authors.lastname: Hession
authors.forename: I
authors.initials: I
authors.lastname: Garcia
authors.forename: J L
authors.initials: JL
authors.lastname: Browning
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D000074049:Cytokine TWEAK; D018076:DNA, Complementary; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048069:Tumor Necrosis Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018925:Chemokines; D000074049:Cytokine TWEAK; D018076:DNA, Complementary; D008024:Ligands; C109743:TNFSF12 protein, human; C491645:Tnfsf12 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors