Regulation of Gene Expression by the Hypoxia-Inducible Factors

Hypoxia-inducible gene regulation by HIF-a. In normoxia, HIF-α is transcriptionally inactive and is rapidly degraded by the ubiquitin (Ub) proteasome pathway. In hypoxia, HIF-α undergoes protein stabilization and translocation from the cytoplasm to the nucleus, where it dimerizes with ARNT and associates with the transcriptional co-activators (as exemplified by CBP/p300) to induce the transcription of HRE-associated genes, such as erythropoietin (EPO) and vascular endothelial growth factor (VEGF). See text for details. CBP, cyclic AMP response element binding protein- (CREB)-binding protein; HRE, hypoxia response element.