The HIF-1α protein is stabilized under hypoxia and translocates to the nucleus to activate gene transcription. Two proline residues of HIF-1α are hydroxylated by prolyl hydroxylase under normoxia. Hydroxylated HIF-1α is bound by the Von Hippel-Lindau (vHL) protein, leading to its ubiquitination and subsequent degradation by the proteasome. In addition, a C-terminal asparagine in the transactivation domain of HIF-1α is hydroxylated by factor inhibiting HIF-1 (FIH) under normoxia. The hydroxylation of HIF-1α blocks its interaction with the transcriptional coactivator p300 and CREB binding protein (CBP), thereby disrupting the proper assembly of HIF-1 at the hypoxia response element (HRE) of its target genes. Without oxygen, the proline and asparagine residues of HIF-1α cannot be hydroxylated; therefore, HIF-1α protein is stabilized, translocates to the nucleus, forms a heterodimer with HIF-β and activates target gene transcription.