Proposed model for Plk3 regulation of HIF-1α. Plk3 directly phosphorylates HIF-1α and facilitates its degradation. Plk3 also phosphorylates PTEN and stabilizes it, thereby increasing overall PTEN activity. PTEN inhibits the PI3K pathway and leads to activation of GSK3β, which phosphorylates and destabilize HIF-1α. Inhibition of HIF-1α by Plk3 through direct and indirect mechanisms results in reduced tumor angiogenesis.