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Figure 1 2.1 Structure of HIF in hypoxic microenvironment In hypoxic conditions, HIF serves as the primary signaling molecule, with HIF-1 exhibiting high sensitivity to low oxygen and serving as the core regulatory molecule in the bodys response to hypoxia ( 2 ) HIF exhibits some expression, yet the synthesized proteins undergo rapid ubiquitination and subsequent degradation via the oxygen sensor prolyl hydroxylases (PHDs)/HIF-1/pVHL pathway ( 2.2 Function of HIF in hypoxic microenvironment Under normoxia conditions, the hydroxylation of Pro402 and Pro564 residues within the ODD domain of HIF-1, catalyzed by oxygen, iron, and 2-oxoglutarate, results in conformational alterations that bolster its affinity for PHD enzyme recognition

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de Mesquita YLL et al

10.1038/nature14029 122 ReyesA