What a difference a hydroxyl makes: mutant IDH, ( R )-2-hydroxyglutarate, and cancer
Brigham and Women's Hospital · Harvard University · +3 more institutions
Abstract
Mutations in metabolic enzymes, including isocitrate dehydrogenase 1 (IDH1) and IDH2, in cancer strongly implicate altered metabolism in tumorigenesis. IDH1 and IDH2 catalyze the interconversion of isocitrate and 2-oxoglutarate (2OG). 2OG is a TCA cycle intermediate and an essential cofactor for many enzymes, including JmjC domain-containing histone demethylases, TET 5-methylcytosine hydroxylases, and EglN prolyl-4-hydroxylases. Cancer-associated IDH mutations alter the enzymes such that they reduce 2OG to the structurally similar metabolite (R)-2-hydroxyglutarate [(R)-2HG]. Here we review what is known about the molecular mechanisms of transformation by mutant IDH and discuss their implications for the…
Citation impact
- FWCI
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- Percentile
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- References
- 187
Authors
2- JLJulie-Aurore LosmanCorresponding
Brigham and Women's Hospital, Harvard University, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center
- WGWilliam G. Kaelin
Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard University, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center
Topics & keywords
- Isocitrate dehydrogenase
- IDH1
- Biology
- IDH2
- Mutant
- Enzyme
- Carcinogenesis
- Biochemistry
- Good health and well-being