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Open AccessJournal ArticleDOI

The Regulation of NF-κB Subunits by Phosphorylation

Frank Christian, +2 more
- 18 Mar 2016 - 
- Vol. 5, Iss: 1, pp 12
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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.

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Citations
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Mechanisms of NF-κB p65 and strategies for therapeutic manipulation.

TL;DR: In this paper, a review of NF-κB p65-mediated signaling is presented, followed by a discussion of strategies that directly target NF-Kb p65 in the context of chronic inflammation.
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Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases.

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Supporting Online Material for Negative Regulation of Toll-Like Receptor Signaling by NF-κB p50 Ubiquitination Blockade

TL;DR: The identification of B cell leukemia (Bcl)–3 as an essential negative regulator of TLR signaling is reported, indicating that the p50 ubiquitination pathway can be selectively targeted to control deleterious inflammatory diseases.
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P2X7 Interactions and Signaling - Making Head or Tail of It

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Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways

TL;DR: It is demonstrated quercetin exerts its anti-cancer effects by modulating ROS, Akt, and NF-κB pathways and could be used as a chemopreventive option as well as in combination with chemotherapeutic drugs to improve clinical outcomes of PCa patients.
References
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Journal ArticleDOI

Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity.

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

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.
Journal ArticleDOI

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

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.
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