G3BP1 and Familial prostate cancer: Here, we identified GTPase Activating Protein (SH3 Domain) Binding Protein 1 (G3BP1) as an interactor and upstream regulator of CUL3SPOP, and it functions as an inhibitor of CUL3SPOP ubiquitin ligase, suggesting a distinctive mode of CUL3SPOP inactivation that aggravates prostate cancer.