USP11 Stabilizes HPV-16E7 and Further Modulates the E7 Biological Activity

Ching-Hui Lin,Hung-Shu Chang,Winston C.Y Yu

doi:10.1074/jbc.m708278200

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.

Highlights

The cellular proteins with which they interact
The C-terminal of USP11 binds to HPV-18E7, but the protein failed to bind to HPV-11E7, a strain not closely linked to cervical cancer
The ubiquitin-mediated protein degradation pathway exerts a wide spectrum of effects and modulates a variety of biological processes, including cell cycle progression, transcriptional regulation, signal transduction, antigen presentation, apoptosis, oncogenesis, preimplantation, endocytosis, vesicle trafficking, and DNA repair [12, 14, 23]

Summary

Introduction

The cellular proteins with which they interact. Among a variety of cellular targets, the effects of E6 and E7 on p53 and pRb as well as on many other cellular proteins have been extensively investigated in the past. We report the identification of another USP11 function in stabilizing HPV-16E7 and further modulate the E7 biological activity. In Vivo Association between 16E7 and USP11—To address a potential interaction between HPV-16E7 and USP11 in mammalian cells, co-immunoprecipitation and Western blot experiments were performed.

Results

Conclusion