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. This evidence concerns the gene VHL and prostate carcinoma.