1. Reactions of 2-OG–dependent dioxygenases inhibited by D2HG.
Reactions of 2-OG–dependent dioxygenases inhibited by D2HG. Reactions are shown for four classes of 2-OG–dependent dioxygenases potentially inhibited by D2HG. All four reactions convert α-KG to succinate and CO2, incorporate O2, and require iron and ascorbate as cofactors. The TET enzymes hydroxylate 5-methylcytosine, which initiates demethylation of these sites. The Jumonji C (JmjC) domain–containing histone demethylases remove methyl groups from the lysine residues of histone proteins, affecting the histone code and altering chromatin structure and transcription. The collagen PHD and LHD hydroxylate proline and lysine residues of collagen during its maturation in the endoplasmic reticulum. These modifications are required for proper folding and glycosylation of collagen. The PHDs controlling the stability of the HIF transcription factors hydroxylate the HIF1α and HIF2α proteins on specific proline residues, targeting them for degradation.
Rob A. Cairns, and Tak W. Mak Cancer Discovery 2013;3:
©2013 by American Association for Cancer Research