Upon validation of the interaction of 18E6 with these ubiquitin ligases in cervical cancer-derived cell lines, we found that the knockdown of ubiquitin ligase F-box protein 4 (FBXO4), together with E6AP knockdown, leads to a dramatic increase in the levels of endogenous HPV-18E6 oncoprotein. The gene discussed is FBXO4; the disease is cervical cancer.