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

作者：Colleran Amy; Collins Patricia E; O' Carroll Christine; Ahmed Abrar; Mao Xicheng; McManus Bettina; Kiely Patrick A; Burstein Ezra; Carmody Ruaidhri J^*

来源：Proceedings of the National Academy of Sciences, 2013, 110(2): 618-623.

DOI：10.1073/pnas.1208446110

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.

• 出版日期2013-1-8