VHL and neoplasm: Since SPOP has been shown to play an oncogenic role in targeting several tumor suppressors such as PTEN and ubiquitin specific peptidase 9 (USP9) under hypoxic conditions or VHL mutant ccRCCs [29, 50], here we demonstrate that under normal conditions or prostate cancer settings, SPOP could directly bind to and degrade PDK1 to repress AKT kinase activity.