Figure 1.

Relationships between select heritable cancers and the hypoxia pathway. Inactivation of von Hippel–Lindau protein (pVHL), succinate dehydrogenase (SDH), or fumarate hydratase (FH) leads to increased expression of genes in the hypoxia pathway. (A) Tricarboxylic acid cycle and its relationship to regulation of hypoxia-inducible factor. (B) Inactivation of pVHL in von Hippel–Lindau disease causes upregulation of genes expressed in the hypoxia pathway through decreased degradation of HIF1-α. (C) Inactivation of SDH in the SDHx hereditary paraganglioma–pheochromocytoma syndromes causes increase in succinate, which inhibits prolyl hydroxylases that would assist in the degradation of HIF. (D) Inactivation of FH in HLRCC causes increase in fumarate, which inhibits prolyl hydroxylases that would assist in the degradation of HIF.