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HIF-1α is hydroxylated on proline residues 402 and/or 564 by prolyl hydroxylases (PHD – 1/2/3), which are tetrameric enzymes with two hydroxylases subunits and two di-sulfide isomerase subunits ( 2+ ), a Krebs cycle intermediate (2 – oxoglutarate), and ascorbate as co-factor to reduce the Fe 3+ ( Figure 1 ) ( In conclusion, hypoxia response through HIF-1α is meant to increase the cell adaptive response to lower oxygen conditions by regulating energy and redox status, thereby promoting cell survival and proliferation
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