NF-κB (nuclear factor κB) controls diverse cellular processes and is frequently misregulated in chronic immune diseases or cancer. The activity of NF-κB is regulated by IκB (inhibitory κB) proteins which control nuclear–cytoplasmic shuttling and DNA binding of NF-κB. In the present paper, we describe a novel role for p65 as a critical regulator of the cellular localization and functions of NF-κB and its inhibitor IκBβ. In genetically modified p65−/− cells, the localization of ectopic p65 is not solely regulated by IκBα, but is largely dependent on the NLS (nuclear localization signal) and the NES (nuclear export signal) of p65. Furthermore, unlike IκBα, IκBβ does not contribute to the nuclear export of p65. In fact, the cellular localization and degradation of IκBβ is controlled by the p65-specific NLS and NES. The results of our present study also reveal that, in addition to stimulus-induced redistribution of NF-κB, changes in the constitutive localization of p65 and IκBβ specifically modulate activation of inflammatory genes. This is a consequence of differences in the DNA-binding activity and signal responsiveness between the nuclear and cytoplasmic NF-κB–IκBβ complexes. Taken together, the findings of the present study indicate that the p65 subunit controls transcriptional competence of NF-κB by regulating the NF-κB/IκBβ pathway.
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Research Article|
February 11 2011
p65 controls NF-κB activity by regulating cellular localization of IκBβ
Taras Valovka;
Taras Valovka
1
*Institute of Biochemistry, Center for Molecular Biosciences, University of Innsbruck, Peter-Mayr-Strasse 1a, A-6020 Innsbruck, Austria
1Correspondence may be addressed to either of these authors (taras.valovka@uibk.ac.at or hottiger@vetbio.uzh.ch).
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Michael O. Hottiger
Michael O. Hottiger
1
†Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
1Correspondence may be addressed to either of these authors (taras.valovka@uibk.ac.at or hottiger@vetbio.uzh.ch).
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Publisher: Portland Press Ltd
Received:
August 05 2010
Revision Received:
November 05 2010
Accepted:
December 16 2010
Accepted Manuscript online:
December 16 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 434 (2): 253–263.
Article history
Received:
August 05 2010
Revision Received:
November 05 2010
Accepted:
December 16 2010
Accepted Manuscript online:
December 16 2010
Citation
Taras Valovka, Michael O. Hottiger; p65 controls NF-κB activity by regulating cellular localization of IκBβ. Biochem J 1 March 2011; 434 (2): 253–263. doi: https://doi.org/10.1042/BJ20101220
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