Cancer Research Center, Nutrition Obesity Research Center, Departments of Medicine and Pharmacology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
Nat Rev Cancer. 2012 Jun 22;12(7):465-77. doi: 10.1038/nrc3256.
The bromodomain is a highly conserved motif of 110 amino acids that is bundled into four anti-parallel α-helices and found in proteins that interact with chromatin, such as transcription factors, histone acetylases and nucleosome remodelling complexes. Bromodomain proteins are chromatin 'readers'; they recruit chromatin-regulating enzymes, including 'writers' and 'erasers' of histone modification, to target promoters and to regulate gene expression. Conventional wisdom held that complexes involved in chromatin dynamics are not 'druggable' targets. However, small molecules that inhibit bromodomain and extraterminal (BET) proteins have been described. We examine these developments and discuss the implications for small molecule epigenetic targeting of chromatin networks in cancer.
溴结构域是一个高度保守的 110 个氨基酸的基序，折叠成四个反平行的α-螺旋，存在于与染色质相互作用的蛋白质中，如转录因子、组蛋白乙酰转移酶和核小体重塑复合物。溴结构域蛋白是染色质的“读取器”；它们招募染色质调节酶，包括组蛋白修饰的“书写器”和“橡皮擦”，以靶向启动子并调节基因表达。传统观点认为，参与染色质动力学的复合物不是“可成药”的靶标。然而，已经描述了抑制溴结构域和末端（BET）蛋白的小分子。我们检查了这些进展，并讨论了它们对癌症中小分子表观遗传靶向染色质网络的影响。
