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

60 Citations (Scopus)

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

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Ubiquitin-Specific Proteases
Phosphotransferases
Tumor Necrosis Factor Receptors
Toll-Like Receptors
Ubiquitination
Ubiquitin
Genes
Immunity
Cytoplasm
Inflammation
Gene Expression
DNA

ASJC Scopus subject areas

  • General

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Deubiquitination of NF-κB by ubiquitin-specific protease-7 promotes transcription. / Colleran, Amy; Collins, Patricia E.; O'Carroll, Christine; Ahmed, Abrar; Mao, Xicheng; McManus, Bettina; Kiely, Patrick A.; Burstein, Ezra; Carmody, Ruaidhrí J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 2, 08.01.2013, p. 618-623.

Research output: Contribution to journalArticle

Colleran, Amy ; Collins, Patricia E. ; O'Carroll, Christine ; Ahmed, Abrar ; Mao, Xicheng ; McManus, Bettina ; Kiely, Patrick A. ; Burstein, Ezra ; Carmody, Ruaidhrí J. / Deubiquitination of NF-κB by ubiquitin-specific protease-7 promotes transcription. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 2. pp. 618-623.
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