Title of article
Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases
Author/Authors
Xu، نويسنده , , Wei and Yang، نويسنده , , Hui and Liu، نويسنده , , Ying and Yang، نويسنده , , Ying and Wang، نويسنده , , Ping and Kim، نويسنده , , Se-Hee and Ito، نويسنده , , Shinsuke and Yang، نويسنده , , Chen and Wang، نويسنده , , Pu and Xiao، نويسنده , , Meng-Tao and Liu، نويسنده , , Li-xia and Jiang، نويسنده , , Wen-qing and Liu، نويسنده , , Jing and Zhang، نويسنده , , Jin-ye and Wang، نويسنده , , Bin and Frye، نويسنده , , Stephen and Zhang، نويسنده , , Yi and Xu، نويسنده , , Yan-hui and Lei، نويسنده , , Qun-ying and Guan، نويسنده , , Kun-Liang and Zhao، نويسنده , , Shi-min and Xiong، نويسنده , , Yue، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2011
Pages
14
From page
17
To page
30
Abstract
Summary
nd IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as α-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 IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.
Journal title
Cancer Cell
Serial Year
2011
Journal title
Cancer Cell
Record number
1337366
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