Beck Hans Christian
Teknologisk Institut, Kolding, Denmark.
Methods Mol Biol. 2010;593:263-82. doi: 10.1007/978-1-60327-194-3_13.
The inhibition of the histone deacetylase enzymes induces hyperacetylation of the histone proteins. This hyperacetylation causes cell cycle arrest and cell death in cancer cells but not in normal cells. Therefore, the development of histone deacetylase inhibitors for the treatment of various cancers has gained tremendous interest in recent years, and many of these inhibitors are currently undergoing clinical trials. Despite intense research, however, the exact molecular mechanisms of action of these molecules remain, to a wide extent, unclear. The recent application of mass spectrometry-based proteomics techniques to histone biology has gained new insight into the function of the nucleosome: Novel posttranslational modifications have been discovered at the lateral surface of the nucleosome. These modifications regulate histone-DNA interactions, adding a new dimension to the epigenetic regulation of nucleosome mobility.
组蛋白脱乙酰酶的抑制会诱导组蛋白的高度乙酰化。这种高度乙酰化会导致癌细胞的细胞周期停滞和细胞死亡,但正常细胞不会。因此,近年来用于治疗各种癌症的组蛋白脱乙酰酶抑制剂的开发引起了极大的关注,目前许多此类抑制剂正在进行临床试验。然而,尽管进行了深入研究,但这些分子的确切作用分子机制在很大程度上仍不清楚。基于质谱的蛋白质组学技术最近在组蛋白生物学中的应用为核小体的功能带来了新的见解:在核小体的侧面发现了新的翻译后修饰。这些修饰调节组蛋白与DNA的相互作用,为核小体移动性的表观遗传调控增添了新的维度。