The Functions of BET Proteins in Gene Transcription of Biology and Diseases.
The Functions of BET Proteins in Gene Transcription of Biology and Diseases.
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BET 蛋白在生物学和疾病基因转录中的功能。
DOI：
10.3389/fmolb.2021.728777
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发表时间：
2021
影响因子：
5
通讯作者：
Zhou MM
中科院分区：
文献类型：
--
作者：
Cheung KL;Kim C;Zhou MM
BET（bromodomain and extra-terminal domain）家族蛋白包括BRD 2、BRD 3、BRD 4和睾丸特异性BRDT，被广泛认为是生物学中的主要转录调节因子。它们的特征在于两个串联的溴结构域（BD），其结合赖氨酸乙酰化的组蛋白和转录因子，将转录因子和共激活因子募集到靶基因位点，并激活RNA聚合酶II机制以进行转录延伸。用BD抑制剂对BET蛋白的药理学抑制已显示为用于治疗许多人类疾病（包括癌症和炎性病症）的有前景的治疗策略。布罗莫结构域蛋白生物学的最新进展进一步揭示了BET蛋白在染色质中基因表达调控中的复杂和多功能。在这篇综述文章中，我们强调了我们目前的理解BET蛋白的功能，介导蛋白质-蛋白质相互作用所需的染色质模板的基因转录和剪接，染色质重塑，DNA复制和DNA损伤修复。我们进一步讨论了个体BET蛋白质、同种型和溴结构域的上下文依赖性激活剂与阻遏物功能，其可用于BET溴结构域抑制剂作为癌症和炎性病症的新兴表观遗传疗法的未来开发。
The BET (bromodomain and extra-terminal domain) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT, are widely acknowledged as major transcriptional regulators in biology. They are characterized by two tandem bromodomains (BDs) that bind to lysine-acetylated histones and transcription factors, recruit transcription factors and coactivators to target gene sites, and activate RNA polymerase II machinery for transcriptional elongation. Pharmacological inhibition of BET proteins with BD inhibitors has been shown as a promising therapeutic strategy for the treatment of many human diseases including cancer and inflammatory disorders. The recent advances in bromodomain protein biology have further uncovered the complex and versatile functions of BET proteins in the regulation of gene expression in chromatin. In this review article, we highlight our current understanding of BET proteins’ functions in mediating protein–protein interactions required for chromatin-templated gene transcription and splicing, chromatin remodeling, DNA replication, and DNA damage repair. We further discuss context-dependent activator vs. repressor functions of individual BET proteins, isoforms, and bromodomains that may be harnessed for future development of BET bromodomain inhibitors as emerging epigenetic therapies for cancer and inflammatory disorders.