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人乳头瘤病毒(HPV)11型和16型E6蛋白对C33A细胞中HPV-11的PE1E4启动子的反式激活活性。

Trans-activating activity of the E6 proteins of the human papillomavirus (HPV) type-11 and -16 on the PE1E4 promoter of HPV-11 in C33A cells.

作者信息

Tomita Y, Asano Y, Shirasawa H

机构信息

Department of Microbiology, School of Medicine, Chiba University, Chuo-Ku, Chiba 260, Japan.

出版信息

Int J Oncol. 1998 Dec;13(6):1253-8. doi: 10.3892/ijo.13.6.1253.

Abstract

We investigated trans-activating effects of the full-length E6 protein of HPV-16 (16E6) and the E6 protein of HPV-11 (11E6) on the PE1E4 promoter of HPV-11 in C33A cells which lack normal function of p53. 16E6 showed no significant activation of the reporter plasmid containing PE1E4 and the upstream sequence, including the long control region (LCR). In contrast, 11E6 activated the promoter in a dose dependent manner, while relatively high doses of 11E6 were required to activate the promoter. When a reporter plasmid, which lacked LCR was used, however, both 16E6 and 11E6 activated the promoter, though high doses of 16E6 suppressed activity. Using deletion plasmids we further showed that 11E6 activated transcriptions from any mutant reporter plasmids as far as the constructs have promoter activities. Finally, we showed that 11E6 enhanced the expression levels of c-fos protein by infection of C33A cells with 11E6-expressing recombinant adenovirus. These findings suggested that E6 proteins of both HPVs would induce similar protein(s) which is required for an efficient transcription of minimum promoter of viral and cellular genes, and that the 16E6 induce additional protein(s) which suppress PE1E4 in the presence or absence of LCR.

摘要

我们研究了人乳头瘤病毒16型(16E6)全长E6蛋白和人乳头瘤病毒11型(11E6)E6蛋白对缺乏p53正常功能的C33A细胞中人乳头瘤病毒11型PE1E4启动子的反式激活作用。16E6对含有PE1E4及包括长控制区(LCR)在内的上游序列的报告质粒未显示出明显的激活作用。相比之下,11E6以剂量依赖方式激活该启动子,不过需要相对高剂量的11E6才能激活启动子。然而,当使用缺乏LCR的报告质粒时,16E6和11E6均能激活启动子,尽管高剂量的16E6会抑制活性。使用缺失质粒我们进一步表明,只要构建体具有启动子活性,11E6就能激活任何突变报告质粒的转录。最后,我们通过用表达11E6的重组腺病毒感染C33A细胞表明,11E6可提高c-fos蛋白的表达水平。这些发现表明,高风险和低风险人乳头瘤病毒的E6蛋白均会诱导病毒和细胞基因最小启动子高效转录所需的相似蛋白,并且16E6会诱导在有或无LCR情况下抑制PE1E4的其他蛋白。

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