title: Deubiquitination of NF-κB by Ubiquitin-Specific Protease-7 promotes transcription.
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.
authors.affiliation: Department of Biochemistry,  University College Cork, Cork,  Ireland.
authors.forename: Amy
authors.initials: A
authors.lastname: Colleran
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Collins
authors.forename: Christine
authors.initials: C
authors.lastname: O'Carroll
authors.forename: Abrar
authors.initials: A
authors.lastname: Ahmed
authors.forename: Xicheng
authors.initials: X
authors.lastname: Mao
authors.forename: Bettina
authors.initials: B
authors.lastname: McManus
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Kiely
authors.forename: Ezra
authors.initials: E
authors.lastname: Burstein
authors.forename: Ruaidhrí J
authors.initials: RJ
authors.lastname: Carmody
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010455:Peptides / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D000076084:Ubiquitin-Specific Peptidase 7; D054875:Ubiquitination
chemical_list: D016328:NF-kappa B; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7