Figure 1.

Schematic diagram of HIF-1α and HIF-1β. Under hypoxic conditions, the PI3K/Akt/mTOR pathway and MAPK (RAF/MEK/ERK) pathway regulate HIF-1α transcriptional activity. The upregulated HIF-1α and HIF-1β form a heterodimer to regulate the expression of HIF-1α target genes with the participation of co-activators CBP/p300. Under normoxia, FIH hydroxylates asparagine (N803) residue within C-TAD to block the cooperative binding of CBP/p300 and C-TAD. PHD, whose activity depends on ferrous, dioxygen and 2-oxoglutarate, is involved in the hydroxylation of HIF-1α. Additionally, VHL, a tumor suppressor, regulates the expression of HIF-1α through ubiquitination and proteasome degradation. HIF-1, hypoxia inducible factor-1; CBP, CREB binding protein; FIH, factor inhibiting HIF-1; PHD, prolyl hydroxylase; VHL, Von Hippel-Lindau; Ub, ubiquitination; HRE, hypoxic response element; TAD, transactivation domain.