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Review
. 2021 Dec;43(12):e2100180.
doi: 10.1002/bies.202100180. Epub 2021 Oct 26.

BRD4 in physiology and pathology: ''BET'' on its partners

Yin Liang  1 , Jieyi Tian  1 , Tao Wu  1
Affiliations
Review

BRD4 in physiology and pathology: ''BET'' on its partners

Yin Liang et al. Bioessays. 2021 Dec.

Abstract

Bromodomain-containing 4 (BRD4), a member of Bromo and Extra-Terminal (BET) family, recognizes acetylated histones and is of importance in transcription, replication, and DNA repair. It also binds non-histone proteins, DNA and RNA, contributing to development, tissue growth, and various physiological processes. Additionally, BRD4 has been implicated in driving diverse diseases, ranging from cancer, viral infection, inflammation to neurological disorders. Inhibiting its functions with BET inhibitors (BETis) suppresses the progression of several types of cancer, creating an impetus for translating these chemicals to the clinic. The diverse roles of BRD4 are largely dependent on its interaction partners in different contexts. In this review we discuss the molecular mechanisms of BRD4 with its interacting partners in physiology and pathology. Current development of BETis is also summarized. Further understanding the functions of BRD4 and its partners will facilitate resolving the liabilities of present BETis and accelerate their clinical translation.

Keywords: BET inhibitors; BRD4; acetylation; disease; interaction partners; transcription.

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References

REFERENCES

    1. Zaware, N., & Zhou, M. M. (2019). Bromodomain biology and drug discovery. Nature Structural & Molecular Biology, 26(10), 870-879.
    1. Wang, C. Y., & Filippakopoulos, P. (2015). Beating the odds: BETs in disease. Trends in Biochemical Sciences, 40(8), 468-479.
    1. Morinière, J., Rousseaux, S., Steuerwald, U., Soler-López, M., Curtet, S., Vitte, A. L., Govin, J., Gaucher, J., Sadoul, K., Hart, D. J., Krijgsveld, J., Khochbin, S., Müller, C. W., & Petosa, C. (2009). Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature, 461(7264), 664-668.
    1. Lambert, J. P., Picaud, S., Fujisawa, T., Hou, H., Savitsky, P., Uusküla-Reimand, L., Gupta, G. D., Abdouni, H., Lin, Z. Y., Tucholska, M., Knight, J., Gonzalez-Badillo, B., St-Denis, N., Newman, J. A., Stucki, M., Pelletier, L., Bandeira, N., Wilson, M. D., Filippakopoulos, P., & Gingras, A. C. (2019). Interactome rewiring following pharmacological targeting of BET bromodomains. Molecular Cell, 73(3), 621-638. e17.
    1. Filippakopoulos, P., & Knapp, S. (2014). Targeting bromodomains: Epigenetic readers of lysine acetylation. Nature Reviews. Drug discovery, 13(5), 337-356.

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