The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology

Trends Immunol. 2009 Aug;30(8):383-91. doi: 10.1016/ Epub 2009 Jul 28.


Nuclear factor (NF)-kappaB has an important role in immunity and inappropriate NF-kappaB activity has been linked with many autoimmune and inflammatory diseases. Multiple mechanisms normally ensure the proper termination of NF-kappaB activation. In this context, the intracellular ubiquitin-editing protein A20 (also known as Tumor Necrosis Factor Alpha-Induced Protein 3 or TNFAIP3) is a key player in the negative feedback regulation of NF-kappaB signaling in response to multiple stimuli. Moreover, A20 also regulates tumor necrosis factor (TNF)-induced apoptosis. Recent genetic studies demonstrate a clear association between several mutations in the human A20 locus and immunopathologies such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and type 1 diabetes. These findings further illustrate the importance of A20 in the resolution of inflammation and the prevention of human disease.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases* / immunology
  • Autoimmune Diseases* / physiopathology
  • DNA-Binding Proteins
  • Gene Expression Regulation*
  • Humans
  • Inflammation* / immunology
  • Inflammation* / physiopathology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Tumor Necrosis Factor-alpha
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3