TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor

Cytokine Growth Factor Rev. Jun-Aug 2003;14(3-4):241-9. doi: 10.1016/s1359-6101(03)00019-4.


The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) was initially described as a member of the tumor necrosis factor (TNF) superfamily in 1997. TWEAK is a cell surface-associated type II transmembrane protein, but a smaller, biologically active form can also be shed into the extracellular milieu. There is one receptor currently known to bind TWEAK with physiological affinity, and it is a type I transmembrane protein that is referred to in the literature as either TWEAK receptor (TweakR) or fibroblast growth factor-inducible 14 (Fn14). TweakR/Fn14 is the smallest member of the TNF receptor (TNFR) superfamily described to date, and it appears to signal via recruitment of several different TNFR-associated factors. TWEAK has multiple biological activities, including stimulation of cell growth and angiogenesis, induction of inflammatory cytokines, and under some experimental conditions, stimulation of apoptosis. In this report, we summarize the results from recent studies focused on the TWEAK cytokine. Although these studies have contributed a significant amount of new information, numerous questions still remain regarding the role of TWEAK in both normal physiology and the pathogenesis of human disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Division
  • Cell Movement
  • Cytokine TWEAK
  • Cytokines / chemistry
  • Cytokines / genetics
  • Cytokines / physiology*
  • Gene Expression
  • Humans
  • Inflammation Mediators / metabolism
  • Mice
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Signal Transduction
  • TWEAK Receptor
  • Tumor Necrosis Factor-alpha / chemistry
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology*
  • Tumor Necrosis Factors


  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cytokine TWEAK
  • Cytokines
  • Inflammation Mediators
  • Receptors, Tumor Necrosis Factor
  • TNFRSF12A protein, human
  • TNFSF12 protein, human
  • TWEAK Receptor
  • Tnfrsf12a protein, mouse
  • Tnfsf12 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factors