Deubiquitination of NF-κB by Ubiquitin-Specific Protease-7 promotes transcription
Deubiquitination of NF-κB by Ubiquitin-Specific Protease-7 promotes transcription
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DOI：
10.1073/pnas.1208446110
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发表时间：
2013-01-08
影响因子：
11.1
通讯作者：
Carmody, Ruaidhri J.
中科院分区：
文献类型：
--
作者：
Colleran, Amy;Collins, Patricia E.;Carmody, Ruaidhri J.
NF-kappa 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-kappa B occurs in the cytoplasm through the kinase activity of the I kappa B kinase complex, which leads to translocation of NF-kappa B to the nucleus. Once in the nucleus, NF-kappa 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-kappa B transcriptional activity. USP7 deubiquitination of NF-kappa B leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-kappa 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-kappa B activity and demonstrate that the deubiquitination of NF-kappa B by USP7 is critical for target gene transcription.
