Banks L, Edmonds C, Vousden K H
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Oncogene. 1990 Sep;5(9):1383-9.
Previous studies have demonstrated that the HPV-16 E7 gene product encodes the major transforming activity of the virus in rodent cell systems. In this study we have generated a series of point mutations affecting the region of HPV-16 E7, which shows homology to adenovirus E1a conserved domain (CD)1. In conjunction with previously described mutants in the region of E7 with similarity to E1a CD2 and SV40 LT, we have investigated three known activities of the E7 protein; transformation, association with the cellular RB protein and induction of cellular DNA synthesis. The results show that RB binding correlates with the ability of E7 to induce cellular DNA synthesis and mediate cell transformation. In addition an unidentified function of E7, which is necessary for transformation of NIH3T3 cells, but does not affect RB binding or the ability to induce cellular DNA synthesis, has also been demonstrated. This study therefore identifies two separate regions of the E7 gene necessary for transformation of established cells. One of these, in the region of E7 which shows similarity to E1a CD2 and LT, is required for RB binding and DNA synthesis. The other region important for transformation, in the N-terminus of E7, is separable from the RB binding/DNA synthesis function.
先前的研究表明，HPV-16 E7基因产物在啮齿动物细胞系统中编码病毒的主要转化活性。在本研究中，我们产生了一系列影响HPV-16 E7区域的点突变，该区域与腺病毒E1a保守结构域（CD）1具有同源性。结合先前描述的E7区域中与E1a CD2和SV40 LT相似的突变体，我们研究了E7蛋白的三种已知活性：转化、与细胞RB蛋白的结合以及诱导细胞DNA合成。结果表明，RB结合与E7诱导细胞DNA合成和介导细胞转化的能力相关。此外，还证明了E7的一种未知功能，它对于NIH3T3细胞的转化是必需的，但不影响RB结合或诱导细胞DNA合成的能力。因此，本研究确定了E7基因中两个对于已建立细胞转化必需的独立区域。其中一个在E7与E1a CD2和LT相似的区域，是RB结合和DNA合成所必需的。另一个对转化重要的区域在E7的N端，与RB结合/DNA合成功能是可分离的。
