Deubiquitination of NF- B by Ubiquitin-Specific Protease-7 promotes transcription

Colleran, A., Collins, P. E., O'Carroll, C., Ahmed, A., Mao, X., McManus, B., Kiely, P. A., Burstein, E. and Carmody, R.J. (2013) Deubiquitination of NF- B by Ubiquitin-Specific Protease-7 promotes transcription. Proceedings of the National Academy of Sciences of the United States of America, 110(2), pp. 618-623. (doi: 10.1073/pnas.1208446110)

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Abstract

NF-κB is the master regulator of the immune response and is responsible for the transcription of hundreds of genes controlling inflammation and immunity. Activation of NF-κB occurs in the cytoplasm through the kinase activity of the IκB kinase complex, which leads to translocation of NF-κB to the nucleus. Once in the nucleus, NF-κB transcriptional activity is regulated by DNA binding-dependent ubiquitin-mediated proteasomal degradation. We have identified the deubiquitinase Ubiquitin Specific Protease-7 (USP7) as a regulator of NF-κB transcriptional activity. USP7 deubiquitination of NF-κB leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-κB, leading to reduced promoter occupancy and reduced expression of target genes in response to Toll-like– and TNF-receptor activation. These findings reveal a unique mechanism controlling NF-κB activity and demonstrate that the deubiquitination of NF-κB by USP7 is critical for target gene transcription.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Carmody, Dr Ruaidhri
Authors: Colleran, A., Collins, P. E., O'Carroll, C., Ahmed, A., Mao, X., McManus, B., Kiely, P. A., Burstein, E., and Carmody, R.J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490

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