Deubiquitination of NF-κB by ubiquitin-specific protease-7 promotes transcription

Amy Colleran, Patricia E. Collins, Christine O'Carroll, Abrar Ahmed, Xicheng Mao, Bettina McManus, Patrick A. Kiely, Ezra Burstein, Ruaidhrí J. Carmody

Research output: Contribution to journalArticle

72 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)618-623
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number2
DOIs
StatePublished - Jan 8 2013

ASJC Scopus subject areas

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