Fig. 1: Schema of regulation of HIF-α degradation and transcriptional activity.
From: The crosstalk between HIFs and mitochondrial dysfunctions in cancer development
Under conditions of normoxia, HIF-1α and HIF-2α are continuously degraded through the key oxygen sensor PHD1–3, especially PHD2 which enables HIF-α to bind to the pVHL. FIH also inhibits HIF-α by binding to HIF-α and impeding thecombination of HIF-α to the transcriptional coactivators CBP and p300. Under hypoxic conditions, the hydroxylation of HIFα is restrained, leading to stabilization of HIF-α. Next, HIF-α dimerizes with HIF-1β to comprise a transcriptional activation complex, which binds to HRE and stimulates the transactivation of target genes.
