Figure 9. HIF-1a activation by hypoxia and stabilizing agents. (A) DMOG is a prolyl hydroxylase enzyme inhibitor, thus preventing ubiquitination and proteasomal degradation of HIF-1a. (B) Oxygen and Fe are required for hydroxylation. However, hypoxia decreases oxygen and Fe availability for these reactions, reducing HIF-1a degradation. (C) Deferoxamine is a Fe chelator, thus decreasing Fe availability for hydroxylation, decreasing HIF-1a degradation. As HIF-1 is accumulating, it translocates into the nucleus, where it interacts with its co-activators (HIF-1b and CBP/p300), engaging in transcriptional activity of downstream genes. HIF-1a, hypoxia-inducible factor-1 alpha; CBP, CREB-binding protein; p300, E1A binding protein p300; Fe, iron; DMOG, dimethyloxalylglycine.
