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Mechanism by which the PTEN-PI3K-AKT-MDM2 signaling axis exerts control over HIF1α degradation in cytoplasm under hypoxic conditions via the MDM2 E3 ligase and 26 S proteasome. PI3K inhibitors block Ser166 phosphorylation of MDM2 resulting in cytoplasmic localization of MDM2; this new signaling pathway is therefore predicted to have therapeutic implications for the control of the HIF1α-VEGF axis in PI3K inhibitor cancer therapeutics.
