The chaperone holdase activity of human papillomavirus E7 oncoprotein

LEONARDO G. ALONSO; MARIA M. GARCÍA-ALAI; CHEMES LUCIA; SALAME MARCELO; GONZALO DE PRAT GAY

Pinamar (Argentina)

Congreso; XLI annual meeting (SAIB); 2005

Sociedad Argentina de Bioquímica (SAIB)

E7 oncoprotein is the major transforming activity in human papillomavirus and shares sequence and functional properties with adenovirus E1A and SV40 T antigen, in particular by targeting the pRb tumor suppressor. HPV 16 E7 forms spherical oligomers that 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-stoichiometric concentrations. We show that the 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 fragment 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