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Biomedicines 2018, 6(1), 16; https://doi.org/10.3390/biomedicines6010016

BET Family Protein BRD4: An Emerging Actor in NFκB Signaling in Inflammation and Cancer

1
INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, Université de Grenoble-Alpes, F-38042 Grenoble, France
2
Pôle Recherche, Grenoble-Alpes University Hospital, F-38043 Grenoble, France
3
Département d’Hématologie Clinique, Dijon University Hospital, F-21000 Dijon, France
4
Département d’Hématologie Clinique, Grenoble-Alpes University Hospital, F-38043 Grenoble, France
5
Centre for Innovation in Cancer Genetics and Epigenetics, Dijon University Hospital, F-21000 Dijon, France
*
Author to whom correspondence should be addressed.
Received: 16 October 2017 / Revised: 31 January 2018 / Accepted: 1 February 2018 / Published: 6 February 2018
(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches)
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Abstract

NFκB (Nuclear Factor-κ-light-chain-enhancer of activated B cells) signaling elicits global transcriptional changes by activating cognate promoters and through genome-wide remodeling of cognate regulatory elements called “super enhancers”. BET (Bromodomain and Extra-Terminal domain) protein family inhibitor studies have implicated BET protein member BRD4 and possibly other BET proteins in NFκB-dependent promoter and super-enhancer modulation. Members of the BET protein family are known to bind acetylated chromatin to facilitate access by transcriptional regulators to chromatin, as well as to assist the activity of transcription elongation complexes via CDK9/pTEFb. BET family member BRD4 has been shown to bind non-histone proteins and modulate their activity. One such protein is RELA, the NFκB co-activator. Specifically, BRD4 binds acetylated RELA, which increases its transcriptional transactivation activity and stability in the nucleus. In aggregate, this establishes an intimate link between NFκB and BET signaling, at least via BRD4. The present review provides a brief overview of the structure and function of BET family proteins and then examines the connections between NFκB and BRD4 signaling, using the inflammatory response and cancer cell signaling as study models. We also discuss the potential of BET inhibitors for relief of aberrant NFκB signaling in cancer, focusing on non-histone, acetyl-lysine binding functions. View Full-Text
Keywords: NFκB; BET inhibition; transcription; chromatin looping; acetylation B cell non-Hodgkin lymphoma NFκB; BET inhibition; transcription; chromatin looping; acetylation B cell non-Hodgkin lymphoma
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hajmirza, A.; Emadali, A.; Gauthier, A.; Casasnovas, O.; Gressin, R.; Callanan, M.B. BET Family Protein BRD4: An Emerging Actor in NFκB Signaling in Inflammation and Cancer. Biomedicines 2018, 6, 16.

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