The Regulation of NF-κB Subunits by Phosphorylation
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TLDR
Importantly, NF-κB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF-σB for therapeutic benefit.Abstract:
The NF-κB transcription factor is the master regulator of the inflammatory response and is essential for the homeostasis of the immune system. NF-κB regulates the transcription of genes that control inflammation, immune cell development, cell cycle, proliferation, and cell death. The fundamental role that NF-κB plays in key physiological processes makes it an important factor in determining health and disease. The importance of NF-κB in tissue homeostasis and immunity has frustrated therapeutic approaches aimed at inhibiting NF-κB activation. However, significant research efforts have revealed the crucial contribution of NF-κB phosphorylation to controlling NF-κB directed transactivation. Importantly, NF-κB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF-κB for therapeutic benefit. This review will focus on the phosphorylation of the NF-κB subunits and the impact on NF-κB function.read more
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References
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Journal ArticleDOI
Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.
Michael Karin,Yinon Ben-Neriah +1 more
TL;DR: Recent progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1.
Journal ArticleDOI
NF-κB, the first quarter-century: remarkable progress and outstanding questions
Matthew S. Hayden,Sankar Ghosh +1 more
TL;DR: Despite the tremendous progress that has been made in understanding the regulation of NF-κB, there is much that remains to be understood and the fundamental questions that remain unanswered after 25 years of study are highlighted.
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Phosphorylation of NF-κB p65 by PKA Stimulates Transcriptional Activity by Promoting a Novel Bivalent Interaction with the Coactivator CBP/p300
TL;DR: Phosphorylation by PKA both weakens the interaction between the N- and C-terminal regions of p65 and creates an additional site for interaction with CBP/p300, which regulates the transcriptional activity of NF-kappa B by modulating its interaction withCBP/ p300.
Journal ArticleDOI
Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression
David E. Nelson,Adaoha E. C. Ihekwaba,M Elliott,James R. Johnson,C. A. Gibney,B. E. Foreman,Glyn Nelson,Violaine Sée,Caroline A. Horton,David G. Spiller,Steven W. Edwards,H. P. McDowell,John Unitt,Elaine Sullivan,Rachel L. Grimley,Neil Benson,David S. Broomhead,Douglas B. Kell,Michael R. H. White +18 more
TL;DR: Single-cell time-lapse imaging and computational modeling of NF-κB (RelA) localization showed asynchronous oscillations following cell stimulation that decreased in frequency with increased IκBα transcription.
Journal ArticleDOI
The Transcriptional Activity of NF-κB Is Regulated by the IκB-Associated PKAc Subunit through a Cyclic AMP–Independent Mechanism
TL;DR: This pathway represents a novel mechanism for the cAMP-independent activation of PKA and the regulation of NF-κB activity and the subsequent phosphorylation of p65 by protein kinase A.