title: USP11 stabilizes HPV-16E7 and further modulates the E7 biological activity.
abstract: HPV-16E7 is a major transforming protein, which has been implicated in the development of cervical cancer. The stability of E7 is thus important to ensure its fully functional status. Using the yeast two-hybrid system, we found that USP11 (ubiquitin-specific protease 11), a member of a protein family that cleaves polyubiquitin chains and/or ubiquitin precursors, interacts and forms a specific complex with HPV-16E7. Our results indicate that the USP11 can greatly increase the steady state level of HPV-16E7 by reducing ubiquitination and attenuating E7 degradation. In contrast, a catalytically inactive mutant of USP11 abolished the deubiquitinating ability and returned E7 to a normal rate of degradation. Moreover, USP11 not only protected E7 from ubiquitination but also influenced E7 function as a modulator of cell growth status. These results suggest that USP11 plays an important role in regulating the levels of E7 protein and subsequently affects the biological function of E7 as well as its contribution to cell transformation by HPV-16E7.
authors.affiliation: National Health Research Institutes, 35 Keyan Rd., Zhunan Town, Miaoli County 350, Taiwan.
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Lin
authors.forename: Hung-Shu
authors.initials: HS
authors.lastname: Chang
authors.forename: Winston C Y
authors.initials: WC
authors.lastname: Yu
mesh_terms: D002472:Cell Transformation, Viral / Q000235:genetics; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D013869:Thiolester Hydrolases / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology
chemical_list: D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C101359:USP11 protein, human; C059731:oncogene protein E7, Human papillomavirus type 16; D013869:Thiolester Hydrolases