McIntyre M C, Ruesch M N, Laimins L A
Department of Microbiology-Immunology, Northwestern University, Chicago, Illinois 60611, USA.
Virology. 1996 Jan 1;215(1):73-82. doi: 10.1006/viro.1996.0008.
The E6 and E7 proteins of the high-risk human papillomaviruses (HPVs) act coordinately to immortalize human keratinocytes. These viral oncoproteins function by binding and altering the activity of cellular proteins which regulate cell cycle progression. Among the proteins bound by E7 are the retinoblastoma protein, Rb, as well as the related p107 and p130 proteins. In addition, E7 binds cyclin A, which regulates transit through the S and G2/M phases of the cell cycle. In this study, we demonstrate that HPV 18 E7 also associates with cyclin E which controls the G1/S transition. E7/cyclin E complexes were immunoprecipitated from E7-expressing cells as well as from cell extracts using GST-E7 fusion proteins. E7 was found to complex with a single form of cyclin E, and the binding was mediated through p107. Both E7/cyclin E and E7/cyclin A complexes exhibit kinase activity through associated cdk2 proteins which can contribute to phosphorylation of p107. The association of E7 with proteins which regulate transit through the cell cycle may provide an additional mechanism by which infection with human papillomaviruses results in cellular hyperproliferation.
高危型人乳头瘤病毒（HPV）的E6和E7蛋白协同作用，使人角质形成细胞永生化。这些病毒癌蛋白通过结合并改变调节细胞周期进程的细胞蛋白的活性来发挥作用。E7所结合的蛋白包括视网膜母细胞瘤蛋白Rb以及相关的p107和p130蛋白。此外，E7还结合细胞周期蛋白A，后者调控细胞周期的S期和G2/M期进程。在本研究中，我们证明HPV 18 E7也与控制G1/S期转换的细胞周期蛋白E相关联。利用GST-E7融合蛋白，从表达E7的细胞以及细胞提取物中免疫沉淀出E7/细胞周期蛋白E复合物。发现E7与单一形式的细胞周期蛋白E形成复合物，且这种结合是通过p107介导的。E7/细胞周期蛋白E复合物和E7/细胞周期蛋白A复合物均通过相关的cdk2蛋白表现出激酶活性，这可能有助于p107的磷酸化。E7与调节细胞周期进程的蛋白之间的关联，可能为人类乳头瘤病毒感染导致细胞过度增殖提供了一种额外的机制。
