HIF regulation

The role of ascorbate, NO, and ROS, as well as other cellular factors, in oxygen sensing is not yet fully clear and requires more investigation. Additionally, other signaling pathways could likely be integrated with HIF regulation as indicated by studies showing that in HIF-la, Thr-796 phosphorylation blocks Asn-803 hydroxylation by FIH (107). 

II. The Role of the von Hippel-Lindau Tumor Suppressor in HIF Regulation... 

Similarly, in mice bearing a conditionally targeted vhl allele, Cre-recombinase-mediated excision results in activation of the HIF pathway in hepatocytes (47). In a further example, some sublines of Chinese hamster ovary-Kl cells selected for activating mutations in the HIF pathway were found to have vhl mutations, and expression of a wild-type human VHL gene restored HIF regulation to normal (48). 

Clinical categories are defined on whether or not hemangioblastoma (HAB) and pheochromocytoma are found in affected kindreds and according to the risk of renal cell carcinoma (RCC). For each clinical category the most fi equently associated mutation is indicated. The effect of the mutations on the ability to restore HIF regulation in stably transfected, VHL-defective renal carcinoma cells is also indicated. 

HIF as master regulator of hypoxia responsive gene expression... 

TF transcription factor, R receptor, Fur ferric uptake regulation protein, NF-kB nuclear factor-kB, AP-1 activator protein-1, Egr-1 early growth response-1, VDR la,25-dihydroxy-vitamin D3 receptor, RXR retinoid X receptor, PPARy peroxisome proliferator-activated receptor y NFAT nuclear factor of activated T-cells, HSF heat shock factor, p53 tumor suppressor p53, HIF-1 hypoxia inducible factor-1. ... 

Lessons from Hypoxia Basic Considerations of HIF-laStability Regulation... 

Fig. 13.2 Stability regulation of HIF-la and as well as FIH activity under normoxia, thus...

Epstein, A. C. et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 2001, 307, 43-54. 

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