Mavromatis K O, Jones D L, Mukherjee R, Yee C, Grace M, Münger K
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892, USA.
Virus Res. 1997 Nov;52(1):109-18. doi: 10.1016/s0168-1702(97)00090-7.
The carboxyl-terminus is necessary for the functional and structural integrity of the human papillomavirus (HPV) E7 oncoprotein. Since many mutations in this domain of E7 result in the formation of unstable proteins, we have evaluated the importance of this region by replacing it with structurally related domains derived from HPV E6 proteins. Biological analysis of these mutant chimeric E7/E6 proteins showed that they retained E7-specific biological activities including cooperation with the ras oncogene to transform primary baby rat kidney cells and transcriptional activation of an E2F responsive reporter plasmid. One of the chimeric proteins was impaired in its ability to physically disrupt pRB/E2F complexes in vitro suggesting that there are defined molecular determinants in the carboxyl-terminus of E7 for this activity. In contrast, none of these proteins exhibited E6-like properties including binding to p53 and/or degradation of associated proteins.
羧基末端对于人乳头瘤病毒（HPV）E7癌蛋白的功能和结构完整性是必需的。由于E7这个结构域中的许多突变会导致不稳定蛋白质的形成，我们通过用源自HPV E6蛋白的结构相关结构域替换它，评估了该区域的重要性。对这些突变嵌合E7/E6蛋白的生物学分析表明，它们保留了E7特异性生物学活性，包括与ras癌基因协同转化原代新生大鼠肾细胞以及E2F反应性报告质粒的转录激活。其中一种嵌合蛋白在体外物理破坏pRB/E2F复合物的能力受损，这表明E7羧基末端存在决定该活性的特定分子决定因素。相比之下，这些蛋白均未表现出E6样特性，包括与p53结合和/或相关蛋白的降解。
