Lu et al. revealed a new signaling network of SKP2-TRAF6-EZH2/ H3K27me3 and found knockout of SKP2 can upregulate TRAF6-mediated and lysine (K) 63-linked ubiquitination of EZH2 for degradation in prostate cancer (PCa) and CRPC cells in vitro and in vivo [92]. The gene discussed is EZH2; the disease is prostate cancer.