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. 2014 Oct 21;5(23):11857–11872. doi: 10.18632/oncotarget.2613

Figure 8. Proposed model of PLD1-mediated HIF1-α stability regulation.

Figure 8

Undernormoxia, PLD1 directly associates with HIF-1α, PHD2 and VHL, thereby coordinating dynamic assembly of PLD-HIF-1α-PHD-VHL, facilitating PHD/VHL mediated polyubiquitination and consequent proteasomal degradation of HIF-1α. Without PLD1, HIF-1α degradation through PHD/VHL would be retarded. Under hypoxia, interactions of PLD1 with the proteinsare disrupted for unknown reasons and PLD1-independent HIF-1α degradation can occur via PHD/VHL, despite hypoxic suppression of PHD activity. This degradative process might occur with less efficiency thanPLD1-independent HIF-1α degradation in normoxia, in which PLD activity is intact. Thickness of the arrows represents relative contribution to degradation of HIF-1α.