IDH1: Linking Metabolism and Epigenetics.

ABSTRACT: Mutations in genes encoding enzymes of the tricarboxylic acid cycle often contribute to cancer development and progression by disrupting cell metabolism and altering the epigenetic landscape. This is exemplified by the isoforms of isocitrate dehydrogenase (IDH1/2), which metabolize isocitrate to α-Ketoglutarate (α-KG). Gain of function mutations in IDH1 or IDH2 result in reduced levels of α-KG as a result of increased formation of D-2-Hydroxyglutarate (2-HG). α-KG is an essential co-factor for certain histone and DNA demethylases, while 2-HG is a competitive inhibitor. These IDH1/2 mutations are thought to result in hypermethylated histones and DNA which in turn alters gene expression and drives cancer progression. While this model seems to be generally accepted in the

SUBMITTER: Raineri S 

PROVIDER: S-EPMC6206167 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature