Fig. 1
From: Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia
Oxygen availability regulates HIF signaling. In normoxia, proline (P) residues on HIFα subunits are hydroxylated by PHDs that marks them for proteasomal degradation. Additionally, FIH-1 mediates hydroxylation of asparagine residues (N) on HIFα to prevent HIF transcriptional activity. Hypoxia impairs the ability of PHDs and FIH-1 to hydroxylate the HIFα subunits, and thus results in the accumulation of this subunit and its heterodimerization with the stable HIFβ subunits. In the nucleus, the HIFα/β complex binds to HRE elements in the HIF target genes and governs their expression in order to adapt the cells to hypoxic conditions