The Chaperone Holdase Activity of Human Papillomavirus E7 oncoprotein

ALONSO, L.G.; SMAL, C.; GARCIA ALAI, M.M.; CHEMES, L.; SALAME, M.; DE PART-GAY, G.

Pinamar, Buenos Aires, Argentina

Congreso; SAIB 41st Reunión Anual, PABMB Xth Congress; 2005

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

E7 oncoprotein is the major transforming activity in human papillomavirus and shares sequence and functional properties with adenovirus E1A and SV40T antigen, in particular by targeting the pRb tumor suppressor. HPV16 E7 forms spherical oligomers thet display chaperone activity in thermal denaturation and chemical refolding assays of two model polypeptide substrates: citrate synthase and luciferase, and it does so at sub-stoichiometrical concentrations. We show that E7 chaperone stably binds the polypeptides en route to denaturation or renaturation and holds them in a near-native state, but does not bind the fully native proteins. However, the E7 oligomers bind native pRb without the requirement of it being partially unfolded. A fragmento containing the N-terminal domain of E7 can interfere with pRb binding but not with the chaperone activity. Thus, the E7 oligomer displays a non-specific chaperone activity that could explain its wide target specificity. The ability to bind up to ~72 molecules of pRb appears as essential either for sequestering pRb from Rb-E2F complexes or for targeting it for proteasome degradation.