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Figure 1 :pVHL/HIF oxygen sensing pathway. In normoxia, HIF- is hydroxylated at two proline residues and an asparagine residue via oxygendependent enzymatic mechanisms. Asparagine hydroxylation blocks HIF- interaction with transcriptional coactivator p300. Proline hydroxylation allows binding of HIF- to wild-type pVHL, which promotes ubiquitination and proteasomal degradation of HIF-. In hypoxia, or in the absence of functional pVHL, HIF- is not degraded, but translocates to the nucleus forming a heterodimer with HIF-/ARNT. The HIF-/ heterodimer activates transcription at hypoxia-responsive elements (HRE), resulting in expression of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor receptor (EGFR), glucose transporters (e.g. GLUT-1), erythropoietin (EPO) and transforming growth factor- (TGF-)

Figure 1 :pVHL/HIF oxygen sensing pathway. In normoxia, HIF- is hydroxylated at two proline residues and an asparagine residue via oxygendependent enzymatic mechanisms. Asparagine hydroxylation blocks HIF- interaction with transcriptional coactivator p300. Proline hydroxylation allows binding of HIF- to wild-type pVHL, which promotes ubiquitination and proteasomal degradation of HIF-. In hypoxia, or in the absence of
functional pVHL, HIF- is not degraded, but translocates to the nucleus forming a heterodimer with HIF-/ARNT. The HIF-/ heterodimer activates transcription at hypoxia-responsive elements (HRE), resulting in expression of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor receptor (EGFR), glucose transporters (e.g. GLUT-1), erythropoietin (EPO) and transforming growth factor- (TGF-)