Ciccolini F, Di Pasquale G, Carlotti F, Crawford L, Tommasino M
Department of Pathology, University of Cambridge, UK.
Oncogene. 1994 Sep;9(9):2633-8.
We have performed comparative studies on the E7 proteins from malignant and non-malignant Human Papillomavirus types HPV 1, 6, 11, 16, 18, 33). GST/E7 fusion proteins from all these HPV types associate with Rb1, p107 and the cyclin A/CDK2 complex. As has been shown for Rb1, the association with p107 and Cyclin A was weaker for the 'low risk' HPV6 and 11 E7 proteins as compared to 'high risk' HPV16, 18 and 33 E7 proteins. In contrast the E7 protein of the benign type HPV1 bound Rb1, p107 and cyclin A with the same affinity as the 'high risk' E7 proteins. The affinities of the E7/Rb1 interaction have been confirmed in vivo by the 'two hybrid' method in the yeast Saccharomyces cerevisiae. Although HPV1 E7 showed the same affinity in vitro and in vivo for Rb1 as the high risk HPV E7s, it did not have the ability to activate the E2F-1 transcription factor inhibited by Rb1, nor did it have any transforming activity when coexpressed with activated ras in primary rodent cells.
我们对来自恶性和非恶性人乳头瘤病毒1、6、11、16、18、33型（HPV）的E7蛋白进行了比较研究。所有这些HPV类型的GST/E7融合蛋白都与Rb1、p107以及细胞周期蛋白A/细胞周期蛋白依赖性激酶2（CDK2）复合物相关联。正如对Rb1的研究所示，与“低风险”HPV6和11型E7蛋白相比，“高风险”HPV16、18和33型E7蛋白与p107和细胞周期蛋白A的关联较弱。相比之下，良性HPV1型的E7蛋白与Rb1、p107和细胞周期蛋白A的结合亲和力与“高风险”E7蛋白相同。E7/Rb1相互作用的亲和力已在酿酒酵母中通过“双杂交”方法在体内得到证实。尽管HPV1 E7在体外和体内对Rb1的亲和力与高风险HPV E7相同，但它没有激活受Rb1抑制的E2F-1转录因子的能力，当与活化的ras在原代啮齿动物细胞中共表达时也没有任何转化活性。
