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Global Translational Medicine

REVIEW ARTICLE
Essential roles of BRD4 in cancer: DNA damage,

transcription regulation, and signal transduction

1,2
Sylvia Y. Sun *
1 Mortimer B. Zuckerman Research Center - Sloan Kettering Institute, 417 E 68 Street, New York,
th
United States of America
2 Department of Dental, New York University, 345 E. 24 Street, New York, United States of America
th

Abstract

During cancer progression, bromodomain and extra-terminal (BET) families regulate
chromatin and recruit enzymes that are associated with chromatin regulation to control
gene expression. The bromodomain-containing protein 4 (BRD4) plays an important
role in DNA damage repair, nuclear factor kappa B (NFκB) signaling, interaction with
c-Myc, and transcription regulation of genes essential in carcinogenesis, as well as
links transcription at enhancers and genes to regulate enhancer transcription. The
colocalization of BRD4 with enhancer and promoter-proximal gene regions enables
the elongation activation at enhancer genes. The inactivation of BRD4 has been
demonstrated to inhibit cancer development, corroborating BRD4 as a promising
therapeutic target. In addition, small-molecule inhibitors targetting functional
domains of BRD4 are under investigation for their potential therapeutic applications
in cancer and other diseases. This review presents an overview of BRD4 function and
its dysfunction in cancer progression, as well as discusses how the potential of BRD4
as a therapeutic target.
*Corresponding author:
Sylvia Y. Sun
(sys9221058@gmail.com) Keywords: BRD4 signaling; Therapy; Cancer
Citation: Sun SY, 2023, Essential
roles of BRD4 in cancer: DNA
damage, transcription regulation,
and signal transduction. Global 1. Introduction
Transl Med, 2(3): 1442.
https://doi.org/10.36922/gtm.1442 Although initially recognized as epigenetic regulators in inflammation and inflammatory
diseases, bromodomain and extra-terminal (BET) proteins, consisting of bromodomain-
Received: August 2, 2023
Accepted: September 22, 2023 containing protein (BRD)2, BRD3, BRD4, and bromodomain testis-specific protein
Published Online: September 29, (BRDT) (Figure 1), are frequently deregulated in cancer, playing a significant role in
2023 tumorigenesis through the promotion of aberrant chromatin modeling and gene
Copyright: © 2023 Author(s). transcription [1,2] . BET families, including BRD4, share two N-terminus domains
This is an Open Access article (N-terminal bromodomain, BD1 and N-terminal bromodomain, BD2) and a C-terminal
distributed under the terms of the
Creative Commons Attribution domain (extra-terminal, ET domain). A high level of conservation exists among the
License, permitting distribution, bromodomains of different species, and the sequences of different BET family members
and reproduction in any medium, are highly similar. The BD domains bind to acetylated lysine residues on histones, while
provided the original work is
properly cited. the ET domain mediates protein-protein interactions and regulates transcriptional
activity [3,4] .
Publisher’s Note: AccScience
Publishing remains neutral with The bromodomains are conserved protein modules which share a high degree of
regard to jurisdictional claims in
published maps and institutional sequence similarity in amino acid; however, each BET protein recruits a distinct set of
affiliations. transcriptional regulatory complexes. Through their unique protein domains outside

Volume 2 Issue 3 (2023) 1 https://doi.org/10.36922/gtm.1442