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Inhibition of JMJD1 proteins by oncometabolites. Shown are the tricarboxylic acid cycle and the production of the oncometabolites succinate, fumarate and 2-hydroxyglutarate that may inhibit catalytic activity of JMJD1 proteins. Loss-of-function mutations in succinate dehydrogenase and fumarate hydratase lead to the accumulation of fumarate and succinate, while neomorphic gain-of-function mutations in isocitrate dehydrogenase cause the reduction of 2-oxoglutarate into 2-hydroxyglutarate.
