Glozak M A, Seto E
H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Oncogene. 2007 Aug 13;26(37):5420-32. doi: 10.1038/sj.onc.1210610.
Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in both cancer initiation and cancer progression. By removal of acetyl groups from histones, HDACs create a non-permissive chromatin conformation that prevents the transcription of genes that encode proteins involved in tumorigenesis. In addition to histones, HDACs bind to and deacetylate a variety of other protein targets including transcription factors and other abundant cellular proteins implicated in control of cell growth, differentiation and apoptosis. This review provides a comprehensive examination of the transcriptional and post-translational mechanisms by which HDACs alter the expression and function of cancer-associated proteins and examines the general impact of HDAC activity in cancer.
组蛋白去乙酰化酶(HDACs)可调节众多参与癌症起始和进展的蛋白质的表达和活性。通过去除组蛋白上的乙酰基,HDACs形成一种不允许转录的染色质构象,从而阻止编码参与肿瘤发生的蛋白质的基因转录。除了组蛋白,HDACs还与多种其他蛋白质靶点结合并使其去乙酰化,这些靶点包括转录因子以及其他与细胞生长、分化和凋亡控制相关的丰富细胞蛋白。本综述全面考察了HDACs改变癌症相关蛋白表达和功能的转录及翻译后机制,并探讨了HDAC活性在癌症中的总体影响。