The mechanisms of IDH mutations in tumorigenesis

被引：33

作者：

Ye, Dan ^{[1
]}

Xiong, Yue ^{[1
,2
,4
]}

Guan, Kun-Liang ^{[1
,3
,5
,6
]}

机构：

[1] Fudan Univ, Inst Biomed Sci, Mol & Cell Biol Lab, Shanghai 200032, Peoples R China

[2] Fudan Univ, Coll Life Sci, Shanghai 200032, Peoples R China

[3] Fudan Univ, Coll Med, Shanghai 200032, Peoples R China

[4] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA

[5] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

来源：

CELL RESEARCH | 2012年 / 22卷 / 07期

关键词：

ONCOMETABOLITE; 2-HYDROXYGLUTARATE; DIFFERENTIATION; PHENOTYPE;

D O I：

10.1038/cr.2012.51

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Tumor-associated mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes result in the loss of normal catalytic activity, the production of alpha-ketoglutarate (alpha-KG), and gain of a new activity, the production of an oncometabolite, R-2-hydroxylglutarate (R-2-HG). New evidence supports previous findings that R-2-HG acts as an antagonist of alpha-KG to competitively inhibit the activity of multiple alpha-KG-dependent dioxygenases, including both histones and DNA demethylases involved in epigenetic control of gene expression and cell differentiation, and also reveals an intriguing new facet of R-2-HG in tumorigenesis.

引用

页码：1102 / 1104

页数：3

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