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Review
. 2022 Mar 25:13:818891.
doi: 10.3389/fphar.2022.818891. eCollection 2022.

A Comprehensive Review of BET Protein Biochemistry, Physiology, and Pathological Roles

Hafiz Akbar Ali  1   2 , Yalan Li  2 , Akram Hafiz Muhammad Bilal  2 , Tingting Qin  1 , Ziqiao Yuan  2 , Wen Zhao  2   3
Affiliations
Review

A Comprehensive Review of BET Protein Biochemistry, Physiology, and Pathological Roles

Hafiz Akbar Ali et al. Front Pharmacol. .

Abstract

Epigenetic modifications, specifically acetylation of histone plays a decisive role in gene regulation and transcription of normal cellular mechanisms and pathological conditions. The bromodomain and extraterminal (BET) proteins (BRD2, BRD3, BRD4, and BRDT), being epigenetic readers, ligate to acetylated regions of histone and synchronize gene transcription. BET proteins are crucial for normal cellular processing as they control cell cycle progression, neurogenesis, differentiation, and maturation of erythroids and spermatogenesis, etc. Research-based evidence indicated that BET proteins (mainly BRD4) are associated with numeral pathological ailments, including cancer, inflammation, infections, renal diseases, and cardiac diseases. To counter the BET protein-related pathological conditions, there are some BET inhibitors developed and also under development. BET proteins are a topic of most research nowadays. This review, provides an ephemeral but comprehensive knowledge about BET proteins' basic structure, biochemistry, physiological roles, and pathological conditions in which the role of BETs have been proven. This review also highlights the current and future approaches to pledge BET protein-related pathologies.

Keywords: BET inhibitors; BET proteins; BRD4; Histone acetylation; epigenetics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
A brief overview of gene transcription: how genetic information in cell transfer from nucleus (right part of figure) to histone tail leading to histone posttranslational modification (PTMs) (left part of figure). Created with BioRender.com.
FIGURE 2
FIGURE 2
Two-dimensional (2D) structural diagram of BET bromodomain (BRD2, BRD3, and BRD4) proteins: All BET bromodomain proteins have common four alpha-helical bundles named as αZ, αA, αB, and αC. αB and αC are connected by a BC loop, and a ZA loop connects αZ, αA helices (based on x-ray crystal structure).
FIGURE 3
FIGURE 3
Summery of functional classification of human bromodomain protein.
FIGURE 4
FIGURE 4
P-TEFb complex-associated gene transcription: BET bromodomain proteins (BRD4, BRDT) recruit positive transcription elongation factor b (P-TEFb) transcription factor at RNA polymerase II leading to phosphorylation of RNA Pol II, which results in gene transcription and elongation. Created with BioRender.com.
See this image and copyright information in PMC

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