(Downloading may take up to 30 seconds.
If the slide opens in your browser, select File -> Save As to save it.)
Click on image to view larger version.


Figure 1


Fig. 1. The HIF1 pathway in normoxia (A) and hypoxia (B). (A) HIF1{alpha} hydroxylation and degradation in the presence of oxygen involves: (1) the independent oxidation-reduction reactions of ascorbate (Asc) and iron (Fe); (2) and (3) prolyl hydroxlyase 2 (PHD2) binding to Fe, 2-oxoglutarate (2OG), and O2; (4) PHD2 hydroxylation of HIF1{alpha}; (5) unbound hydroxylated HIF1{alpha} moving in the cell cytoplasm; (6) the von Hippel Lindau (VHL)-Elongin B (EB)-Elongin C (EC) complex ubiquitylating HIF1{alpha}; and (7) HIF1{alpha} degradation. A change in shading of HIF1{alpha} indicates addition of a hydroxyl group. (B) In hypoxia, HIF1{alpha} enters the nucleus, where hydroxylation, but no degradation occurs. (1) and (2) PHD2 binding to Fe, 2OG and Asc, but not O2. (3) The protein inhibitor of growth 4 (ING4) binding to PHD2 may regulate HIF1{alpha} transcriptional activity and (4) block HIF1{alpha}-HIF1ß binding. When HIF1{alpha}-HIF1ß binding occurs, the HIF1 dimer can transcriptionally activate genes at the hypoxia response element (HRE) site.