遗传 ›› 2013, Vol. 35 ›› Issue (3): 241-254.doi: 10.3724/SP.J.1005.2013.00241

• 综述 •    下一篇

赖氨酸甲基转移酶PR-SET7及其生物学功能

梁新全, 杜贻鹏, 王东来, 杨洋   

  1. 北京大学基础医学院, 北京 100191
  • 收稿日期:2012-05-16 修回日期:2012-07-27 出版日期:2013-03-20 发布日期:2013-03-25
  • 通讯作者: 杨洋 E-mail:yangsh@bjmu.edu.cn
  • 基金资助:

    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)和国家基础科学人才培养基金(编号:J1030831/J0108)资助

The biological functions of lysine methyltransferase PR-SET7

LIANG Xin-Quan , DU Yi-Peng , WANG Dong-Lai , YANG Yang   

  1. School of Basic Medical Sciences, Peking University, Beijing 100191, China
  • Received:2012-05-16 Revised:2012-07-27 Online:2013-03-20 Published:2013-03-25

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(Lysine methyltransferase, 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ERa、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。

关键词: PR-SET7, H4K20, 单甲基化作用, 细胞周期, 基因转录

Abstract: PR-SET7 (also named SET8 or KMT5a) is a sole lysine methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20me1) in higher eukaryotes. The abundance of PR-SET7 is dynamically mediated by the distinct E3 ubiquitin ligases in different cell cycle phases. PR-SET7 is closely related to the regulation of cell proliferation, and the H4K20me1 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, Wnt and p53. PR-SET7 is also essential for individual development and partici-pates in the formation of genomic imprinting. Moreover, PR-SET7 has been reported to promote tumorigenesis and metastasis, suggesting 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.

Key words: H4K20, monomethylation, cell cycle, gene transcription, PR-SET7