Biochemical and structure-function analyses of the HPVE7 oncoprotein

Abstract

The human papillomavirus E7 oncoprotein is the main transforming agent of this important pathogen. Although its primary action is binding and targeting the retinoblastoma tumour suppressor protein, over two decades of research showed a much more complex mode of action where multiple cellular partners and cellular events take place before ultimate progression into carcinogenesis. In this chapter we describe the HPV16 E7 protein in biochemical terms in an attempt to understand some of the various interactions in which this protein participates. We describe its multiple equilibria and conformational species in solution that can explain some of its puzzling promiscuous binding activities and review the few interactions that have been addressed by biochemical and mechanistic approaches to date. We finally discuss the cellular localization of E7 conformers, how they influence its antigenic capacity, and how they can be exploited in therapeutic applications.