Kinase Networks Regulate Metabolism: I'D(H1) Never Have Guessed!

Mutations in isoforms of isocitrate dehydrogenase (IDH) enzymes are described in multiple cancers and both mutant and wild-type IDH are important for the generation and maintenance of tumors, but how their activity is regulated is poorly understood. An article in this issue of Cancer Discovery identifies a novel posttranslational mechanism of IDH1 regulation involving phosphorylation of specific tyrosine residues by a network of kinases that alter the specificity of substrate and cofactor binding, dimer formation, and ultimately enzyme activity.See related article by Chen et al., p. 756.