MDM2 and cancer: Additionally, the E3 ligases SKP2 (S-phase 2 kinase-associated protein 2) and CUL4A (Cullin-4A) were downregulated after 24 h of CPYPP treatment, but MDM2 was enhanced, while the deubiquitinase CYLD, Cyclin D1, and p21 were upregulated (Supplemental Fig. S10J), suggesting an operative mechanism in UPS against cancer cell growth [34, 35].