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. Author manuscript; available in PMC: 2015 Jul 25.
Published in final edited form as: Chem Biol Interact. 2014 May 10;0:82–88. doi: 10.1016/j.cbi.2014.05.001

Figure 3. The hypoxia-inducible HIF-1α signaling pathway.

Figure 3

Under normal oxygen conditions (21% oxygen), HIF-1α proteins are proline hydroxylated by PHDs, ubiquitinated by VHL proteins and ultimately degraded via the proteaseome. Hypoxic conditions (< 6% oxygen) diminish PHD function and thus lead to HIF-1α stabilization. Non-hydroxylated HIF-1α translocates to the nucleus and dimerizes with ARNT. The HIF-1α:ARNT transcription factor complex binds to HRE sequences in target gene promoters. HRE: hypoxia response element; PHD: prolyl hydroxylase domain-containing enzymes; p300/CBP: histone actelytransferase p300/CREB-binding protein; VHL: von Hippel-Lindau tumor suppressor.