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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein
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Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein

机译:人类乳头瘤病毒16型E7癌蛋白对M2型丙酮酸激酶活性的调节

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摘要

We report here that the E7 oncoprotein encoded by the oncogenic human papillomavirus (HPW type 16 binds to the glycolytic enzyne 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 glyco- Iytic flux in tumor cells. The glycolytic intermcdiate fructose l,6-bisphosphate induces the reassociation of the dimeric to the tetrameric form of MZ-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-1 6 E7 mutants and the nononcogenic RPV-ll subtype suggest that the interaction of HPV-16 E7 with MZ-PK may be linked to the transforming potential of the viral oncoprotein.
机译:我们在这里报告说,致癌性人乳头瘤病毒(HPW 16型与糖酵解酶型M2丙酮酸激酶(M2-PK)结合)编码的E7癌蛋白。M2.PK以四聚体的形式与其底物磷酸烯醇丙酮酸和对磷酸烯醇丙酮酸具有低亲和力的二聚体形式,并且两个构象之间的过渡调节肿瘤细胞中的糖酵解通量;糖酵解中间产物果糖1,6-二磷酸酯诱导二聚体与MZ-PK的四聚体形式重新缔合。尽管果糖1,6-二磷酸水平显着增加,但在实验细胞系中E7的表达却使平衡向二聚状态转移;对HPV-1 6 E7突变体和非致癌性RPV-II亚型的研究表明,HPV的相互作用具有MZ-PK的-16 E7可能与病毒癌蛋白的转化潜力有关。

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