Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
Curr Med Chem. 2020;27(33):5583-5598. doi: 10.2174/0929867326666190731141055.
CBP and p300 are two closely related Histone Acetyltransferases (HATs) that interact with numerous transcription factors and act to increase the expression of their target genes. Both proteins contain a bromodomain flanking the HAT catalytic domain that is important in binding of CBP/p300 to chromatin, which offers an opportunity to develop protein-protein interaction inhibitors. Since their discovery in 2006, CBP/p300 bromodomains have attracted much interest as promising new epigenetic targets for diverse human diseases, including inflammation, cancer, autoimmune disorders, and cardiovascular disease. Herein, we present a comprehensive review of the structure, function, and inhibitors of CBP/p300 bromodomains developed in the last several years, which is expected to be beneficial to relevant studies.
CBP 和 p300 是两种密切相关的组蛋白乙酰转移酶 (HATs)，它们与许多转录因子相互作用，以增加其靶基因的表达。这两种蛋白质都含有一个溴结构域，该结构域侧翼是 HAT 催化结构域，对于 CBP/p300 与染色质的结合非常重要，这为开发蛋白质-蛋白质相互作用抑制剂提供了机会。自 2006 年发现以来，CBP/p300 的溴结构域作为多种人类疾病（包括炎症、癌症、自身免疫性疾病和心血管疾病）有希望的新的表观遗传靶点，引起了广泛关注。本文综述了近年来 CBP/p300 溴结构域的结构、功能和抑制剂的研究进展，有望为相关研究提供有益的参考。
