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


ABSTRACT: NF-?B 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-?B occurs in the cytoplasm through the kinase activity of the I?B kinase complex, which leads to translocation of NF-?B to the nucleus. Once in the nucleus, NF-?B 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-?B transcriptional activity. USP7 deubiquitination of NF-?B leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-?B, 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-?B activity and demonstrate that the deubiquitination of NF-?B by USP7 is critical for target gene transcription.

SUBMITTER: Colleran A 

PROVIDER: S-EPMC3545798 | biostudies-other | 2013 Jan

REPOSITORIES: biostudies-other

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Deubiquitination of NF-κB by Ubiquitin-Specific Protease-7 promotes transcription.

Colleran Amy A   Collins Patricia E PE   O'Carroll Christine C   Ahmed Abrar A   Mao Xicheng X   McManus Bettina B   Kiely Patrick A PA   Burstein Ezra E   Carmody Ruaidhrí J RJ  

Proceedings of the National Academy of Sciences of the United States of America 20121224 2


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 Pr  ...[more]

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