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Regulation of NF-κB signaling by the A20 deubiquitinase

Cellular & Molecular Immunology volume 9, pages 123–130 (2012)Cite this article

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.

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Acknowledgements

The laboratory of E W Harhaj is supported by NIH grant nos. PO1CA128115, RO1CA135362 and RO1GM083143.

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  1. Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, 33136, FL, USA

    Noula Shembade & Edward W Harhaj

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Shembade, N., Harhaj, E. Regulation of NF-κB signaling by the A20 deubiquitinase. Cell Mol Immunol 9, 123–130 (2012). https://doi.org/10.1038/cmi.2011.59

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