赖氨酸甲基转移酶PR-SET7及其生物学功能  

The biological functions of lysine methyltransferase PR-SET7

作　　者：梁新全[1] 杜贻鹏[1] 王东来[1] 杨洋[1] 

机构地区：[1]北京大学基础医学院,北京100191

出　　处：《遗传》2013年第3期241-254,共14页Hereditas（Beijing)

基　　金：国家科技部基金项目(编号:2012CB517500);国家自然科学基金项目(编号:81071676;31261140372);国家基础科学人才培养基金(编号:J1030831/J0108)资助

摘　　要：PR-SET7,也称SET8、KMT5a,是现今发现唯一能够特异性单甲基化H4K20的赖氨酸甲基转移酶(Lysinemethyltransferase,KMT)。在细胞周期不同时相PR-SET7的含量处于波动之中,主要受泛素连接酶调节。PR-SET7与细胞增殖密切相关,其催化的组蛋白H4K20单甲基化修饰在DNA复制、染色体固缩及细胞周期检验点激活中发挥重要调控作用。PR-SET7缺失将导致DNA损伤,细胞周期阻滞,甚至发生细胞凋亡。而且,PR-SET7可以调节ER、Wnt、p53等多种基因的转录,进而影响相应基因的表达。PR-SET7为个体发育所必需,并参与了基因组印记的形成。另外,PR-SET7还能促进肿瘤的发生和转移,有望成为肿瘤治疗的新靶点。文章主要从PR-SET7的结构、对组蛋白修饰的调节、在细胞周期、基因转录过程中的调控,以及其在个体发育和肿瘤发生中的作用等方面综述了PR-SET7的研究进展。PR-SET7 （also named SET8 or KMT5a） is a sole lysine methyltransferase that catalyzes monomethylation of histone H4 lysine 20 （H4K20mel） in higher eukaryotes. The abundance of PR-SET7 is dynamically mediated by the dis- tinct E3 ubiquitin ligases in different cell cycle phases. PR-SET7 is closely related to the regulation of cell proliferation, and the H4K20mel catalyzed by PR-SET7 has been implicated in regulating the diverse biological processes, including DNA replication, chromosome condensation and the activation of DNA replication checkpoints. Loss of PR-SET7 results in mas- sive DNA damage, cell cycle arrest and induction of apoptosis. In addition, PR-SET7 involves in regulating the transcrip- tion of several genes, such as ERa, Writ andp53. PR-SET7 is also essential for individual development and participates in the formation of genomic imprinting. Moreover, PR-SET7 has been reported to promote tumorigenesis and metastasis, sug- gesting that PR-SET7 may be a potential target for cancer treatment. In this review, we focus on analyzing the structure of PR-SET7 and factors influencing histone modification on regulation of PR-SET7, and discuss the mechanisms by which PR-SET7 modulates cell-cycle progression, gene transcription, individual development and tumorigenesis.

关 键 词：PR-SET7 H4K20 单甲基化作用 细胞周期 基因转录 

分 类 号：Q55[生物学—生物化学]