Tumor-suppressive and anti-metastatic roles of UBE2L6 in vivo have not been described, and we found are mediated in melanoma by the ubiquitin-conjugating function of UBE2L6, working cooperatively with the E3 ligase UBR4, to induce EZH2 ubiquitination and protein degradation [53]. The gene discussed is UBR4; the disease is melanoma.