Regulation of NF-κB signaling by the A20 deubiquitinase

Noula Shembade, Edward W. Harhaj

Research output: Contribution to journalReview article

95 Scopus citations

Abstract

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 Iδ °B 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.

Original languageEnglish (US)
Pages (from-to)123-130
Number of pages8
JournalCellular and Molecular Immunology
Volume9
Issue number2
DOIs
StatePublished - Mar 1 2012

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Keywords

  • A20
  • inflammation
  • NF-κB
  • ubiquitin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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