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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(徐薇)^[1,2]Yang, Hui^[1,2];Liu, Ying^[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^[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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