溴结构域蛋白4的结构和功能及其抑制剂在肿瘤研究中的应用

Advances of structure and mechanisms of bromodomain- containing protein 4 and its related research in tumors

摘要:

溴结构域和超末端结构域(bromodomain and extraterminal domain, Bet)家族是表观基因组的调节因子，也是肿瘤细胞生存所依赖的肿瘤相关基因表达的关键驱动因子。溴结构域蛋白4 (bromodomain-containing protein 4, Brd4)是溴域和端外蛋白家族中的一员，通常识别乙酰化组蛋白，并定位于目的基因的启动子或增强子区域，启动并维持肿瘤相关基因的表达。Brd4与多种转录因子调控和染色质修饰密切相关，并参与DNA损伤修复、维持端粒功能，从而维持肿瘤细胞的存活。本文围绕Brd4蛋白的结构、功能及其抑制剂在肿瘤研究中的应用进行综述。

Abstract:

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.