组蛋白去乙酰化酶抑制剂的研究进展

核小体是真核生物染色质的基本单位,通过对组蛋白核心的N-端的乙酰化、甲基化、磷酸化、遍在蛋白化的修饰作用而影响细胞的功能。组蛋白乙酰化酶(histone acetylase HAT)及组蛋白去乙酰化酶(Histone Deacetylases HDAC)之间的动态平衡控制着染色质的结构和基因表达。当组蛋白去乙酰化水平增加,乙酰化水平相对降低,即会导致正常的细胞周期与代谢行为的改变而诱发肿瘤,及神经退行性变。组蛋白去乙酰化酶抑制剂(Histone Deacetylases-inhibitor HDACi)目前是国内外研究的热点。其中,曲古霉素A(Trichostatin A TSA),是最早发现的天然组蛋白去乙酰化酶抑制剂;伏立诺他(Suberoylanilide Hydroxamic Acid SAHA)已经美国FDA批准用于治疗皮肤T细胞淋巴瘤。本文就HDACi分类及其功能出发综述HDACi的作用机制及研究进展。

Progress on Histone Deacetylase Inhibitors

Nucleosome is the basic unit of eukaryotic chromatin. The acetylation, methylation, phosphorylatin modification ofhistone N-terminal, will affect the cell function. The balance of histone acetylase and deacetylase in epigenetic modifications is critical tothe regulation of chromatin structure and gene expression. When increased the levels of histone deacetylation , acetylation levelsrelatively reduction that would affect the normal cell cycle and metabolic changes in behavior induced tumors and neurodegeneration.Histone deacetylase inhibitors have become the hot field of researches. TrichostatinA (TSA), is one of the earliest discovered naturalhistone deacetylase inhibitor; Vorinostat (Suberoylanilide Hydroxamic Acid SAHA) has been approved by the FDA for the treatment ofcutaneous T-cell lymphoma. This review describes the HDACi classification, and function. Summary HDACi mechanism of action andresearch progress.