Alqahtani Ali, Choucair Khalil, Ashraf Mushtaq, Hammouda Danae M, Alloghbi Abduraham, Khan Talal, Senzer Neil, Nemunaitis John
Department of Internal Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH, 43614, USA.
Division of Hematology & Medical Oncology, Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH, 43614, USA.
Future Sci OA. 2019 Jan 29;5(3):FSO372. doi: 10.4155/fsoa-2018-0115. eCollection 2019 Mar.
Histone lysine acetylation is critical in regulating transcription. Dysregulation of this process results in aberrant gene expression in various diseases, including cancer. The bromodomain, present in several proteins, recognizes promotor lysine acetylation and recruits other transcription factors. The bromodomain extra-terminal (BET) family of proteins consists of four conserved mammalian members that regulate transcription of oncogenes such as and the NUT fusion oncoprotein. Targeting the acetyl-lysine-binding property of BET proteins is a potential therapeutic approach of cancer. Consequently, following the demonstration that thienotriazolodiazepine small molecules effectively inhibit BET, clinical trials were initiated. We thus discuss the mechanisms of action of various BET inhibitors and the prospects for their clinical use as cancer therapeutics.
组蛋白赖氨酸乙酰化在调节转录过程中至关重要。该过程的失调会导致包括癌症在内的各种疾病中出现异常基因表达。存在于多种蛋白质中的溴结构域可识别启动子赖氨酸乙酰化并募集其他转录因子。溴结构域额外末端（BET）蛋白家族由四个保守的哺乳动物成员组成，它们调节诸如 和NUT融合癌蛋白等癌基因的转录。靶向BET蛋白的乙酰赖氨酸结合特性是一种潜在的癌症治疗方法。因此，在证实噻吩并三唑二氮杂卓小分子能有效抑制BET之后，便启动了临床试验。我们在此讨论各种BET抑制剂的作用机制及其作为癌症治疗药物的临床应用前景。
