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

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.

Pubmed ID: 23267096


  • Colleran A
  • Collins PE
  • O'Carroll C
  • Ahmed A
  • Mao X
  • McManus B
  • Kiely PA
  • Burstein E
  • Carmody RJ


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

Publication Data

January 8, 2013

Associated Grants

  • Agency: NIDDK NIH HHS, Id: R01 DK073639
  • Agency: NIDDK NIH HHS, Id: R01 DK073639

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • NF-kappa B
  • NIH 3T3 Cells
  • Peptides
  • Real-Time Polymerase Chain Reaction
  • Transcription, Genetic
  • Transfection
  • Tumor Necrosis Factor-alpha
  • Ubiquitin Thiolesterase
  • Ubiquitination