摘要
组蛋白甲基化是一种重要的表观遗传性修饰方式,是一个可逆的动态调节过程。组蛋白去甲基化酶家族中组蛋白去甲基化酶4能催化去除组蛋白赖氨酸残基甲基标记,调节染色质的结构,参与精细调控基因转录,维持染色质的活性和非活性平衡。组蛋白去甲基化酶4异常可能导致细胞增殖、分化、个体发育、能量代谢及肿瘤发生发展等多种生物进程异常。研究显示组蛋白去甲基化酶4可作为新的药物靶标。本文就组蛋白去甲基化酶4家族的结构、作用机制、在疾病发生发展进程中的生物学功能及特异性抑制剂开发的最新研究进展作一综述。
Histone lysine methylation, a covalent histone modification, plays a central role in epigenetic regulation networks of genome function. The histone lysine demethylase （KDM） 4 sub- family eatalyzes the removal of methyl marks from histone lysine residues to epigenetieally regulate ehromatin structure, cell cycle, genome integrity and gene expression. Dysregulation of the KDM4 demethylases is associated with abnormities of cell proliferation and differentiation, development and metabolism, as well as tumorigenesis. Furthermore, KDM4 demethylases are promising druggable tar- gets due to their enzymatic activity. In this review, we summarize recent findings regarding the struc- tures and regulatory mechanisms of the KDM4 proteins, as well as our current understanding of their alterations and roles in human disease. We also review the reported KDM4 inhibitors and discuss their potential as therapeutic agents.
出处
《转化医学杂志》
2014年第1期13-18,共6页
Translational Medicine Journal
基金
Karmanos Cancer Institute-SRIG
江苏师范大学校基金(09XLA08
11XLR25)
关键词
组蛋白去甲基化酶
组蛋白去甲基化酶4
肿瘤
Lysine-specific demethylase
Lysine-specific demethylase 4 （KDM4）
Tumour
