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. 2022 Jan;10(2):109. doi: 10.21037/atm-21-4222

Figure 1.

Figure 1

HIF-1α degradation and activation. Under normoxia, the conserved proline residues 402 and 564 of HIF-1α are hydroxylated by PHD. Subsequently, pVHL mediates ubiquitination of HIF-1α, which is then degraded by the proteasome. FIH1 and ROS also affect HIF-1α activity: the former blocks the binding of HIF to CBP/p300 and inhibits transcriptional activation of HIF-1α; the latter inhibits acetylation of HIF-1α by preventing activation of PHD. Under hypoxia, hydroxylation and acetylation of HIF-1α are inhibited, which stabilizes HIF-1α and allows it to form dimers with HIF-1β (ARNT), bind with CBP/p300 and form transcription initiation complexes and activate target genes. HIF-1α, hypoxia-inducible factor-1 alpha; PHD, proline hydroxylase domain; pVHL, von Hippel Lindau protein; FIH1, factor-inhibiting HIF-1; ROS, reactive oxygen species; CBP, cyclic adenosine monophosphate response element-binding protein; p300, coactivator acetyltransferase; ARNT, aryl-hydrocarbon-nuclear receptor translocator.