Regulation of TNFRSF and innate immune signalling complexes by TRAFs and cIAPs

Cell Death Differ. 2010 Jan;17(1):35-45. doi: 10.1038/cdd.2009.114.


There have been a number of recent discoveries relating to the functions of inhibitors of apoptosis (IAPs) and TNF receptor-associated factors (TRAFs) in regulating signalling from TNF receptor superfamily (TNFRSF) members and some tantalizing glimpses into a wider area of influence, that of innate immune signalling. Discoveries relating to the function of these ubiquitin E3 ligases in regulating signalling from the eponymous member of the family, TNF-R1, are dealt with superbly in a separate review by Wertz and Dixit and so we will confine our discussion to the subset of the TNFRSF that does not contain a death domain (DD). In line with the available data we will divide the review into two parts, the first is restricted to the role of TRAFs 2 and 3 and cIAPs in regulating TNFRSF signalling, whereas the second will be more speculative, asking what role IAPs and TRAFs have in innate immune signalling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • DNA-Binding Proteins / metabolism
  • Immunity, Innate*
  • Inhibitor of Apoptosis Proteins / metabolism
  • NF-kappa B / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / metabolism*
  • Ubiquitin-Protein Ligases / metabolism


  • DNA-Binding Proteins
  • Inhibitor of Apoptosis Proteins
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Ubiquitin-Protein Ligases
  • Protein-Serine-Threonine Kinases
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • NF-kappa B kinase