A Selective Inhibitor and Probe of the Cellular Functions of Jumonji C Domain-Containing Histone Demethylases

被引：118
|
作者：
Luo, Xuelai [1 ]
Liu, Yongxiang [1 ]
Kubicek, Stefan [2 ,3 ,4 ,5 ]
Myllyharju, Johanna [6 ]
Tumber, Anthony [7 ]
Ng, Stanley [7 ,8 ]
Che, Ka Hing [7 ,8 ]
Podoll, Jessica [1 ]
Heightman, Tom D. [7 ]
Oppermann, Udo [7 ,8 ]
Schreiber, Stuart L. [2 ,3 ,4 ]
Wang, Xiang [1 ]
机构：
[1] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA
[2] Broad Inst Harvard, Howard Hughes Med Inst, Cambridge, MA 02142 USA
[3] MIT, Cambridge, MA 02142 USA
[4] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
[5] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria
[6] Univ Oulu, Dept Med Biochem & Mol Biol, Bioctr Oulu, Oulu Ctr Cell Matrix Res, FIN-90014 Oulu, Finland
[7] Univ Oxford, Struct Genom Consortium, Headington OX3 7DQ, England
[8] Oxford Biomed Res Unit, NIHR, Botnar Res Ctr, Oxford OX3 7LD, England
来源：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2011年 / 133卷 / 24期
基金：
英国惠康基金;
关键词：
OXYGEN SENSING PATHWAY; LYSINE DEMETHYLASES; PROLYL; 4-HYDROXYLASES; SUBSTRATE-SPECIFICITY; STRUCTURAL INSIGHTS; MODIFYING ENZYMES; FAMILY; CELLS; LSD1; DEACETYLASES;
D O I：
10.1021/ja201597b
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Histone methylations are important chromatin marks that regulate gene expression, genomic stability, DNA repair, and genomic imprinting. Histone demethylases are the most recent family of histone-modifying enzymes discovered. Here, we report the characterization of a small-molecule inhibitor of Jumonji C domain-containing histone demethylases. The inhibitor derives from a structure-based design and preferentially inhibits the subfamily of trimethyl lysine demethylases. Its methyl ester prodrug, methylstat, selectively inhibits Jumonji C domain-containing histone demethylases in cells and may be a useful small-molecule probe of chromatin and its role in epigenetics.
引用
收藏
页码：9451 / 9456
页数：6
相关论文
共 50 条
  • [21] Ascorbic acid modulates immune responses through Jumonji-C domain containing histone demethylases and Ten eleven translocation (TET) methylcytosine dioxygenase
    Maity, Jeet
    Majumder, Satyabrata
    Pal, Ranjana
    Saha, Bhaskar
    Mukhopadhyay, Prabir Kumar
    BIOESSAYS, 2023, 45 (11)
  • [22] The Histone Demethylase Jumonji Domain-Containing Protein 3 (JMJD3) As Central Mediator of Fibroblast Activation
    Bergmann, Christina
    Brandt, Amelie
    Dees, Clara
    Zhang, Yun
    Chen, Chih-Wei
    Mallano, Tatjana
    Wohlfahrt, Thomas
    Liang, Ruifang
    Kagwiria, Rosebeth
    Bozec, Aline
    Rieker, Ralf
    Abraham, David
    Ramming, Andreas
    Distler, Oliver
    Schett, Georg
    Distler, Joerg
    ARTHRITIS & RHEUMATOLOGY, 2017, 69
  • [23] Kinetic and inhibition studies on human Jumonji-C (JmjC) domain-containing protein 5
    Tumber, Anthony
    Salah, Eidarus
    Brewitz, Lennart
    Corner, Thomas P.
    Schofield, Christopher J.
    RSC CHEMICAL BIOLOGY, 2023, 4 (06): : 399 - 413
  • [24] A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin
    Souto, Jose A.
    Sarno, Federica
    Nebbioso, Angela
    Papulino, Chiara
    Alvarez, Rosana
    Lombino, Jessica
    Perricone, Ugo
    Padova, Alessandro
    Altucci, Lucia
    de Lera, Angel R.
    FRONTIERS IN CHEMISTRY, 2020, 8
  • [25] Jumonji domain-containing protein 6 protein and its role in cancer
    Yang, Jing
    Chen, Siyuan
    Yang, Yanfei
    Ma, Xuelei
    Shao, Bin
    Yang, Shengyong
    Wei, Yuquan
    Wei, Xiawei
    CELL PROLIFERATION, 2020, 53 (02)
  • [26] Critical role of histone demethylase Jumonji domain-containing protein 3 in the regulation of neointima formation following vascular injury
    Luo, XiaoLing
    Yang, Di
    Wu, Weijun
    Long, Fen
    Xiao, ChenXi
    Qin, Ming
    Law, Betty YuenKwan
    Suguro, Rinkiko
    Xu, Xin
    Qu, LeFeng
    Liu, XinHua
    Zhu, Yi Zhun
    CARDIOVASCULAR RESEARCH, 2018, 114 (14) : 1894 - 1906
  • [27] The histone demethylase Jumonji domain-containing protein 3 (JMJD3) regulates fibroblast activation in systemic sclerosis
    Bergmann, Christina
    Brandt, Amelie
    Merlevede, Benita
    Hallenberger, Ludwig
    Dees, Clara
    Wohlfahrt, Thomas
    Poetter, Sebastian
    Zhang, Yun
    Chen, Chih-Wei
    Mallano, Tatiana
    Liang, Ruifang
    Kagwiria, Rosebeth
    Kreuter, Alexander
    Pantelaki, Ioanna
    Bozec, Aline
    Abraham, David
    Rieker, Ralf
    Ramming, Andreas
    Distler, Oliver
    Schett, Georg
    Distler, Joerg H. W.
    ANNALS OF THE RHEUMATIC DISEASES, 2018, 77 (01) : 150 - +
  • [28] Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development
    Canovas, Sebastian
    Cibelli, Jose B.
    Ross, Pablo J.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (07) : 2400 - 2405
  • [29] Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases
    Hong, SunHwa
    Cho, Young-Wook
    Yu, Li-Rong
    Yu, Hong
    Veenstra, Timothy D.
    Ge, Kai
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (47) : 18439 - 18444
  • [30] A Jumonji C(Jmj) domain-containing protein negatively regulates RANKL-mediated osteoclastogenesis.
    Kim, Seon-Young
    Kim, Hye-Jin
    Jung, Do Won
    Park, Jong-Wan
    Chun, Yang-Sook
    JOURNAL OF BONE AND MINERAL RESEARCH, 2017, 32 : S146 - S146
12345