This study lays the groundwork to better understand the mechanism of how PA28γ activates T-L activity, which could inform efforts to design inhibitors of PA28γ function that could be used to specifically treat PA28γ-overexpressed cancers and 20S proteasome T-L site stimulating drugs that could be used to treat PolyQ neurodegenerative diseases. This evidence concerns the gene PSME3 and cancer.