Hypoxia and its impact on the tumour microenvironment of gastroesophageal cancers

Figure 3 Regulation of hypoxia-inducible factor 1-α by oxygen levels and von Hippel Lindau protein. Hydroxylation by oxygen-dependent prolyl hydroxylase domain enzymes triggers recognition by the E3 ubiquitin ligase von Hippel Lindau, ensuring proteasomal degradation. In the non-von Hippel Lindau protein dependent pathway, induction of Factor Inhibiting hypoxia-inducible factor (HIF) leads to hydroxylation of an asparagine residue preventing HIF1-α from localizing with the co-activators p300 and CBP, hence disabling transcriptional activation[30]. The HIF pathway functions to conduct and orchestrate the cellular response to low oxygen availability[24,25]. HRE: Hypoxia response element; ARNT: Aryl hydrocarbon receptor nuclear translocator; PHD: Prolyl hydroxylase domain enzymes; VHL: Von Hippel Lindau; HIF1-α: Hypoxia-inducible factor 1-α; FIH: Factor inhibiting hypoxia-inducible factor.