The Role of Hypoxia Inducible Factor-1 in Hepatocellular Carcinoma

Figure 2

Oxygen-dependent regulation of HIF-1α activity. Under normoxic conditions, HIF-1α subunit is rapidly hydroxylated by prolyl hydroxylases (PHDs) and binds to von Hippel-Lindau protein (pVHL), resulting in the rapid ubiquitination of HIF-1α and subsequent proteasomeal degradation. Under hypoxic conditions, HIF-1α is stabilized and translocated into the nucleus by importin α/β and dimerizes with HIF-1β. The HIF heterodimer affects transcription of target genes by binding to a hypoxia response element (HRE) in the upstream promoter region after cooperation with transcriptional coactivators such as p300/CBP.