TY - JOUR
T1 - Deubiquitination of NF-κB by ubiquitin-specific protease-7 promotes transcription
AU - Colleran, Amy
AU - Collins, Patricia E.
AU - O'Carroll, Christine
AU - Ahmed, Abrar
AU - Mao, Xicheng
AU - McManus, Bettina
AU - Kiely, Patrick A.
AU - Burstein, Ezra
AU - Carmody, Ruaidhrí J.
PY - 2013/1/8
Y1 - 2013/1/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84872202679&partnerID=8YFLogxK
U2 - 10.1073/pnas.1208446110
DO - 10.1073/pnas.1208446110
M3 - Article
C2 - 23267096
AN - SCOPUS:84872202679
SN - 0027-8424
VL - 110
SP - 618
EP - 623
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 2
ER -