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The HIF pathway. (Left) Under normoxic conditions, PHD2 hydroxylates proline 531 of HIF-2α, which can then be recognized by VHL, targeting it for ubiquitylation and degradation. (Right) Under hypoxic conditions, PHD2 cannot hydroxylate HIF α subunits, allowing it to be stabilized and translocate to the nucleus to dimerize with ARNT; the HIF-α-ARNT complex in the nucleus triggers transcriptional activation at hypoxia response elements (HREs).
