Fig. 3. Regulatory factors of 2OGDDs for HIF1α stabilization. Succinate, fumarate, and mitochondrial ROS inhibit PHD activation, leading to HIF1α stability. Conversely, 2OG, Fe2+, and ascorbate are required for PHD activation, followed by VHL-induced HIF1α ubiquitination. FIH is more sensitive to oxygen than VHL. Like PHD, ascorbate also activates FIH, which leads to asparaginyl hydroxylation, leading in turn to the destabilization of HIF1α.
© 2019 International Journal of Stem Cells