Regulation of NF-κB signaling by the A20 deubiquitinase

Cell Mol Immunol. 2012 Mar;9(2):123-30. doi: 10.1038/cmi.2011.59. Epub 2012 Feb 20.


The NF-κB transcription factor is a central mediator of inflammatory and innate immune signaling pathways. Activation of NF-κB is achieved by K63-linked polyubiquitination of key signaling molecules which recruit kinase complexes that in turn activate the IκB kinase (IKK). Ubiquitination is a highly dynamic process and is balanced by deubiquitinases that cleave polyubiquitin chains and terminate downstream signaling events. The A20 deubiquitinase is a critical negative regulator of NF-κB and inflammation, since A20-deficient mice develop uncontrolled and spontaneous multi-organ inflammation. Furthermore, specific polymorphisms in the A20 genomic locus predispose humans to autoimmune disease. Recent studies also indicate that A20 is an important tumor suppressor that is inactivated in B-cell lymphomas. Therefore, targeting A20 may form the basis of novel therapies for autoimmune disease and lymphomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Humans
  • I-kappa B Kinase / immunology
  • Immunity, Innate / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Mice
  • Mice, Knockout
  • NF-kappa B / immunology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Signal Transduction / immunology
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tumor Suppressor Proteins / immunology*
  • Ubiquitin-Protein Ligases / immunology*
  • Ubiquitination / immunology


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