Ali Hafiz Akbar, Li Yalan, Bilal Akram Hafiz Muhammad, Qin Tingting, Yuan Ziqiao, Zhao Wen
Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Front Pharmacol. 2022 Mar 25;13:818891. doi: 10.3389/fphar.2022.818891. eCollection 2022.
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.
表观遗传修饰,特别是组蛋白乙酰化,在正常细胞机制和病理状态的基因调控及转录中起决定性作用。含溴结构域和额外末端(BET)蛋白(BRD2、BRD3、BRD4和BRDT)作为表观遗传阅读器,与组蛋白的乙酰化区域结合并同步基因转录。BET蛋白对正常细胞过程至关重要,因为它们控制细胞周期进程、神经发生、分化以及红细胞生成和精子发生等的成熟过程等。基于研究的证据表明,BET蛋白(主要是BRD4)与多种病理疾病相关,包括癌症、炎症、感染、肾脏疾病和心脏疾病等。为对抗与BET蛋白相关的病理状况,已经开发出一些BET抑制剂,还有一些正在研发中。BET蛋白是当前研究最多的课题之一。本综述提供了关于BET蛋白的基本结构、生物化学、生理作用以及已证实BET蛋白发挥作用的病理状况的简短但全面的知识。本综述还强调了应对与BET蛋白相关病理的当前和未来方法。