Fig. 4.

The oncometabolites, 2-HG and fumarate, inhibit PHD activity to promote angiogenesis. PHDs promote the proteosomal degradation of HIF-1α. Therefore, inhibition of PHDs by oncometabolites results in activation of HIF-1α. Subsequently, HIF-1α forms a heterodimer with HIF-1β whereafter the complex translocates to the nucleus to promote VEGF gene expression. Abbreviations: HIF-1α (hypoxia inducible factor-1 alpha), PHD (prolyl hydroxylase), α-KG (alpha-ketoglutarate), 2-HG (2-hydroxyglutarate), pVHL (Von Hippel Lindau protein), HIF-1β (hypoxia inducible factor-1 beta), VEGF (vascular endothelial growth factor). Figure created using BioRender