磷酸化BRD4：转录可塑性与药物靶向作用
Phospho-BRD4: transcription plasticity and drug targeting.
作者信息
Chiang Cheng-Ming
机构信息
Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
出版信息
Drug Discov Today Technol. 2016 Mar;19:17-22. doi: 10.1016/j.ddtec.2016.05.003. Epub 2016 Jul 18.
Abstract
BRD4 is an epigenetic regulator and transcription cofactor whose phosphorylation by CK2 and dephosphorylation by PP2A modulates its function in chromatin targeting, factor recruitment, and cancer progression. While the bromodomains of BET family proteins, including BRD4, BRD2, BRD3 and BRDT, have been the primary targets of small compounds such as JQ1, I-BET and MS417 that show promising anticancer effects against some hematopoietic cancer and solid tumors, drug resistance upon prolonged treatment necessitates a better understanding of alternative pathways underlying not only the resistance but also persistent BET protein dependence for identifying new targets and effective combination therapy strategies.
摘要
BRD4是一种表观遗传调节因子和转录辅因子，其被CK2磷酸化以及被PP2A去磷酸化可调节其在染色质靶向、因子募集和癌症进展中的功能。虽然包括BRD4、BRD2、BRD3和BRDT在内的BET家族蛋白的溴结构域一直是JQ1、I-BET和MS417等小分子化合物的主要靶点，这些化合物对某些血液系统癌症和实体瘤显示出有前景的抗癌作用，但长期治疗后的耐药性使得有必要更好地了解不仅是耐药性而且是持续的BET蛋白依赖性背后的替代途径，以识别新靶点和有效的联合治疗策略。
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