title: Regulation of NF-κB signaling by the A20 deubiquitinase.
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 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.
authors.affiliation: Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Noula
authors.initials: N
authors.lastname: Shembade
authors.forename: Edward W
authors.initials: EW
authors.lastname: Harhaj
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051550:I-kappa B Kinase / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D025521:Tumor Suppressor Proteins / Q000276:immunology*; D044767:Ubiquitin-Protein Ligases / Q000276:immunology*; D054875:Ubiquitination / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051550:I-kappa B Kinase; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3