Hypoxia inducible factor in hepatocellular carcinoma: A therapeutic target

Figure 1 Structure of hypoxia-inducible factor-1. Hypoxia-inducible factor (HIF)-1 is a heterodimer comprising HIF-1α and HIF-1β. Both subunits contain basic helix-loop helix (bHLH) motifs and PER-ARNT-SIM (PAS) domains needed for dimerization and binding to hypoxia response elements (HREs) in the promoter region of target regions. HIF-1α contains two transactivation domains: the NH₂-terminal transactivation domain (N-TAD), located on the oxygen-dependent degradation domain (ODDD), and the carboxy-terminal transactivation domain (C-TAD). Both transactivation domains are essential for promoting HIF-1α target gene transcription. Hydroxylation of N-TAD and C-TAD of HIF-1α leads to inhibition of HIF-1α target gene transcription.