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　　这篇文章署名有意思

　　作者：trus

　　两位senior author分别来自美国两个单位，同时又是复旦大学内的不同系
所。更好玩的是，一位第一作者，却出现了三位共同第二作者。

　　这是不是中国人民智慧的体现？

　　Science 10 April 2009:
　　Vol. 324. no. 5924, pp. 261 - 265
　　DOI: 10.1126/science.1170944
　　Prev | Table of Contents | Next
　　REPORTS
　　Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic 
Activity and Induce HIF-1
　　Shimin Zhao,1,2 Yan Lin,1* Wei Xu,1,2* Wenqing Jiang,1,2* Zhengyu 
Zha,1 Pu Wang,1,2 Wei Yu,1,2 Zhiqiang Li,4 Lingling Gong,5 Yingjie 
Peng,6 Jianping Ding,6 Qunying Lei,1,3 Kun-Liang Guan,1,3,7Yue 
Xiong1,2,8
　　Heterozygous mutations in the gene encoding isocitrate 
dehydrogenase-1 (IDH1) occur in certain human brain tumors, but their 
mechanistic role in tumor development is unknown. We have shown that 
tumor-derived IDH1 mutations impair the enzyme's affinity for its 
substrate and dominantly inhibit wild-type IDH1 activity through the 
formation of catalytically inactive heterodimers. Forced expression of 
mutant IDH1 in cultured cells reduces formation of the enzyme product, 
-ketoglutarate (-KG), and increases the levels of hypoxia-inducible 
factor subunit HIF-1, a transcription factor that facilitates tumor 
growth when oxygen is low and whose stability is regulated by -KG. The 
rise in HIF-1 levels was reversible by an -KG derivative. HIF-1 levels 
were higher in human gliomas harboring an IDH1 mutation than in tumors 
without a mutation. Thus, IDH1 appears to function as a tumor 
suppressor that, when mutationally inactivated, contributes to 
tumorigenesis in part through induction of the HIF-1 pathway.
　　1 Molecular and Cell Biology Laboratory, Institute of Biomedical 
Sciences, Fudan University, 130 Dong-An Road, Shanghai 200032, China.
　　2 School of Life Sciences, Fudan University, 220 Han-Dan Road, 
Shanghai 200433, China.
　　3 Department of Biological Chemistry, School of Medicine, Fudan 
University, 130 Dong-An Road, Shanghai 200032, China.
　　4 Department of Neurosurgery, Zhongnan Hospital, Wuhan University, 
Wuhan 430071, China.
　　5 Department of Pathology, Zhongnan Hospital, Wuhan University, 
Wuhan 430071, China.
　　6 State Key Laboratory of Molecular Biology, Institute of 
Biochemistry and Cell Biology, Shanghai Institute for Biological 
Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 
200031, China.
　　7 Department of Pharmacology and Moores Cancer Center, University 
of California San Diego, La Jolla, CA 92093, USA.
　　8 Department of Biochemistry and Biophysics, Lineberger 
Comprehensive Cancer Center, University of North Carolina at Chapel 
Hill, NC 27599, USA.
　　* These authors contributed equally to this work.


　　To whom correspondence should be addressed. E-mail: 
kuguan@ucsd.edu (K.-L.G.); yxiong@email.unc.edu (Y.X.)

(XYS20091204)

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