Caldeira S, de Villiers E M, Tommasino M
Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Oncogene. 2000 Feb 10;19(6):821-6. doi: 10.1038/sj.onc.1203375.
Studies on human papillomavirus type 16 have demonstrated that the product of the early gene, E7, plays a key role in the immortalization and malignant transformation of the host cell. Several of the biological activities of HPV16 E7 are mediated by inactivation of the members of the pocket protein family, pRb, p107 and p130. In this study, we have characterized the in vitro properties of five E7 proteins from benign and malignant HPV types (10, 32, 48, 54, 77). We show that these E7 proteins associate with pRb and p107 with different efficiencies. All E7s increased the proliferative rate of immortalized rodent fibroblasts cultured in 10% calf serum containing medium. This property is completely independent of their ability to associate with the pocket proteins. Furthermore, all E7s, except HPV10 E7, stimulate G1/S progression and activated the cyclin E and cyclin A promoter in the absence of growth factors. This activity also does not correlate with the E7-efficiency of binding the pocket proteins. Together these data provide evidence that different E7s alter the regulation of the cell cycle by diverse mechanism(s). Finally, this comparative analysis of the different E7 proteins demonstrates that the oncogenicity of a HPV type is not determined by the ability of E7 to associate with the pocket proteins.
对16型人乳头瘤病毒的研究表明，早期基因E7的产物在宿主细胞的永生化和恶性转化中起关键作用。HPV16 E7的几种生物学活性是通过使口袋蛋白家族成员pRb、p107和p130失活来介导的。在本研究中，我们已对来自良性和恶性HPV类型（10、32、48、54、77）的五种E7蛋白的体外特性进行了表征。我们发现这些E7蛋白与pRb和p107结合的效率不同。所有E7蛋白均提高了在含10%小牛血清的培养基中培养的永生化啮齿动物成纤维细胞的增殖速率。这一特性完全独立于它们与口袋蛋白结合的能力。此外，除HPV10 E7外，所有E7蛋白在缺乏生长因子的情况下均能刺激G1/S期进程并激活细胞周期蛋白E和细胞周期蛋白A启动子。这一活性也与E7结合口袋蛋白的效率无关。这些数据共同证明，不同的E7蛋白通过多种机制改变细胞周期调控。最后，对不同E7蛋白的这一比较分析表明，HPV类型的致癌性并非由E7与口袋蛋白结合的能力所决定。
