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Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of alpha-Ketoglutarate-Dependent Dioxygenases  期刊论文   WOS高被引论文

  • 编号:
    0473f277-38d1-4e4f-8582-2adde73cf970
  • 作者:
    Xu, Wei[1,2];Yang, Hui[1,2];Liu, Ying(刘颖)[3]Yang, Ying[1];Wang, Ping[1];Kim, SeHee[9];Ito, Shinsuke[9,11];Yang, Chen[6];Wang, Pu(王璞)[1,2]Xiao, MengTao[1,2];Liu, Lixia[5];Jiang, Wenqing[1,2];Liu, Jing[6];Zhang, Jinye[2];Wang, Bin[4];Frye, Stephen[10];Zhang, Yi[9,11,12];Xu, Yanhui(徐彦辉)[1]Lei, Qunying(雷群英)[2,5]Guan, KunLiang[1,2,5,7,8];Zhao, Shimin(赵世民)[1,2]Xiong, Yue[1,2,9,12];
  • 语种:
    英文
  • 期刊:
    CANCER CELL ISSN:1535-6108 2011 年 19 卷 1 期 (17 - 30) ; JAN 18
  • 收录:
  • 摘要:

    1DH1 and 1DH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple alpha-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as alpha-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and 1DH2 mutations reduce alpha-KG and accumulate an alpha-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.

  • 推荐引用方式
    GB/T 7714:
    Xu Wei,Yang Hui,Liu Ying, et al. Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of alpha-Ketoglutarate-Dependent Dioxygenases [J].CANCER CELL,2011,19(1):17-30.
  • APA:
    Xu Wei,Yang Hui,Liu Ying,Yang Ying,&Xiong Yue.(2011).Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of alpha-Ketoglutarate-Dependent Dioxygenases .CANCER CELL,19(1):17-30.
  • MLA:
    Xu Wei, et al. "Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of alpha-Ketoglutarate-Dependent Dioxygenases" .CANCER CELL 19,1(2011):17-30.
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