title: Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein.
abstract: We report here that the E7 oncoprotein encoded by the oncogenic human papillomavirus (HPV) type 16 binds to the glycolytic enzyme type M2 pyruvate kinase (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 phosphoenolpyruvate, 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 form 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 fructose 1,6-bisphosphate levels. Investigations of HPV-16 E7 mutants and the nononcogenic HPV-11 subtype suggest that the interaction of HPV-16 E7 with M2-PK may be linked to the transforming potential of the viral oncoprotein.
authors.affiliation: Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Abt. F0301, INF 242, D-69120 Heidelberg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Zwerschke
authors.forename: S
authors.initials: S
authors.lastname: Mazurek
authors.forename: P
authors.initials: P
authors.lastname: Massimi
authors.forename: L
authors.initials: L
authors.lastname: Banks
authors.forename: E
authors.initials: E
authors.lastname: Eigenbrodt
authors.forename: P
authors.initials: P
authors.lastname: Jansen-Dürr
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011487:Protein Conformation; D011770:Pyruvate Kinase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection