Modulation of type M-2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein

We report here that the E7 oncoprotein encoded by the oncogenic human papil lomavirus (HPV) type 16 binds to the glycolytic enzyme type M-2 pyruvate ki nase (M2-PK). M2-PK occurs in a tetrameric form with a high affinity to its substrate phosphoenolpyruvate and a dimeric form with a low affinity to ph osphoenolpyruvate, and the transition between both conformations regulates the glycolytic flux in tumor cells. The glycolytic intermediate fructose 1, 6-bisphosphate induces the reassociation of the dimeric to the tetrameric f orm of M2-PK. The expression of E7 in an experimental cell line shifts the equilibrium to the dimeric state despite a significant increase in the fruc tose 1,6-bisphosphate levels. Investigations of HPV-16 E7 mutants and the n ononcogenic HPV-11 subtype suggest that the interaction of HPV-16 E7 with M 2-PK may be linked to the transforming potential of the viral oncoprotein.