Padmanabhan Balasundaram, Mathur Shruti, Manjula Ramu, Tripathi Shailesh
Department of Biophysics, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560 029, India.
J Biosci. 2016 Jun;41(2):295-311. doi: 10.1007/s12038-016-9600-6.
The bromodomains and extra-terminal domain (BET) family proteins recognize acetylated chromatin through their bromodomains (BDs) and help in regulating gene expression. BDs are chromatin 'readers': by interacting with acetylated lysines on the histone tails, they recruit chromatin-regulating proteins on the promoter region to regulate gene expression and repression. Extensive efforts have been employed by scientific communities worldwide to identify and develop potential inhibitors of BET family BDs to regulate protein expression by inhibiting acetylated histone (H3/H4) interactions. Several small molecule inhibitors have been reported, which not only have high affinity but also have high specificity to BET BDs. These developments make BET family proteins an important therapeutic targets for major diseases such as cancer, neurological disorders, obesity and inflammation. Here, we review and discuss the structural biology of BET family BDs and their applications in major diseases.
溴结构域和额外末端结构域（BET）家族蛋白通过其溴结构域（BDs）识别乙酰化染色质，并有助于调节基因表达。BDs是染色质“读取器”：通过与组蛋白尾巴上的乙酰化赖氨酸相互作用，它们在启动子区域招募染色质调节蛋白，以调节基因表达和抑制。全球科学界已付出巨大努力来鉴定和开发BET家族BDs的潜在抑制剂，以通过抑制乙酰化组蛋白（H3/H4）相互作用来调节蛋白质表达。已经报道了几种小分子抑制剂，它们不仅对BET BDs具有高亲和力，而且具有高特异性。这些进展使BET家族蛋白成为癌症、神经疾病、肥胖和炎症等主要疾病的重要治疗靶点。在此，我们综述并讨论BET家族BDs的结构生物学及其在主要疾病中的应用。
