Expanding TRAF function: TRAF3 as a tri-faced immune regulator

Nat Rev Immunol. 2011 Jun 10;11(7):457-68. doi: 10.1038/nri2998.


Tumour necrosis factor receptor (TNFR)-associated factor (TRAF) proteins are essential components of signalling pathways activated by TNFR or Toll-like receptor (TLR) family members. Acting alone or in combination, the seven known TRAFs control many biological processes, including cytokine production and cell survival. The function of one TRAF in particular, TRAF3, remained elusive for many years. Recent work has revealed that TRAF3 is a highly versatile regulator that positively controls type I interferon production, but negatively regulates mitogen-activated protein kinase activation and alternative nuclear factor-κB signalling. In this Review, we discuss our current understanding of the role of TRAF3 in TNFR and TLR signalling pathways, and its role in disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Interferon Type I / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • NF-kappa B / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction / immunology
  • Signal Transduction / physiology*
  • TNF Receptor-Associated Factor 3 / immunology
  • TNF Receptor-Associated Factor 3 / physiology*
  • Toll-Like Receptors / metabolism*


  • Interferon Type I
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Factor 3
  • Toll-Like Receptors
  • Mitogen-Activated Protein Kinases