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Fig. 1 | Clinical and Translational Medicine

Fig. 1

From: Mitochondria, cholesterol and cancer cell metabolism

Fig. 1

Regulation of HIF1α transcriptional activity. a In normoxia, PHD hydroxylates HIF1α in several proline and asparagine residues, with 2-OG, ascorbate and Fe3+, acting as cofactors for the reaction. Hydroxyted HIF1α binds with high affinity to the E3 ubiquitin-ligase pVHL and HIF1α becomes ubiquitinated, marking it for proteasomal degradation. Through this mechanism, HIF1α is kept at very low concentrations and transcriptionally inactive. b In low O2 conditions, the activity of PHD is inhibited due to lack of oxygen, resulted in no hydroxylation nor ubiquitination of HIF1α. These events lead to the HIF1α protein stabilization which can translocate to the nucleus where it forms a complex with HIF1β and recruits CBP/p300 to the promoter of HIF1α target genes, activating the transcription of a vast array of genes responsible of glycolysis, angiogenesis and cell death resistance which are involved in tumor progression

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