| First Author | Colleran A | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 2 | Pages | 618-23 |
| PubMed ID | 23267096 | Mgi Jnum | J:193284 |
| Mgi Id | MGI:5468074 | Doi | 10.1073/pnas.1208446110 |
| Citation | Colleran A, et al. (2013) Deubiquitination of NF-kappaB by Ubiquitin-Specific Protease-7 promotes transcription. Proc Natl Acad Sci U S A 110(2):618-23 |
| abstractText | NF-kappaB 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-kappaB occurs in the cytoplasm through the kinase activity of the IkappaB kinase complex, which leads to translocation of NF-kappaB to the nucleus. Once in the nucleus, NF-kappaB 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-kappaB transcriptional activity. USP7 deubiquitination of NF-kappaB leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-kappaB, 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-kappaB activity and demonstrate that the deubiquitination of NF-kappaB by USP7 is critical for target gene transcription. |
