en
Scientific article
English

TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis

Published inThe Journal of biological chemistry, vol. 272, no. 51, p. 32401-32410
Publication date1997
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.

Keywords
  • Adenocarcinoma/metabolism/ pathology
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins/genetics/ metabolism/secretion
  • Chemokines/secretion
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17
  • 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
Affiliation Not a UNIGE publication
Citation (ISO format)
CHICHEPORTICHE, Yves et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. In: The Journal of biological chemistry, 1997, vol. 272, n° 51, p. 32401–32410. doi: 10.1074/jbc.272.51.32401
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Identifiers
ISSN of the journal0021-9258
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