Mechanisms of human papillomavirus E2-mediated repression of viral oncogene expression and cervical cancer cell growth inhibition
Mechanisms of human papillomavirus E2-mediated repression of viral oncogene expression and cervical cancer cell growth inhibition
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DOI：
10.1128/jvi.74.8.3752-3760.2000
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发表时间：
2000-04-01
影响因子：
5.4
通讯作者：
Sakai, H
中科院分区：
文献类型：
--
作者：
Nishimura, A;Ono, T;Sakai, H
乳头瘤病毒E2基因产物在病毒复制中起关键作用。E2具有多种功能，包括（i）转录激活和抑制病毒启动子和（ii）增强病毒DNA复制。以前有报道，E2抑制乳头瘤病毒阳性宫颈癌细胞系的生长。在本研究中，我们研究了E2生长抑制的机制。我们发现E2的转录激活功能是抑制HeLa细胞生长以及抑制病毒E6/E7启动子转录所必需的。先前假设E6/E7启动子的转录抑制是由于E2结合其邻近E6/E7启动子的同源位点并置换其他细胞转录因子。在这项研究中，我们报告的转录激活功能的结合E2转录活性模板的要求。
The papillomavirus E2 gene product plays a pivotal role in viral replication. E2 has multiple functions, including (i) transcriptional activation and repression of viral promoters and (ii) the enhancement of viral DNA replication. It was previously reported that E2 suppressed the growth of papillomavirus-positive cervical carcinoma cell lines. In the present study, we investigated the mechanisms of E2 growth inhibition. We found that the transcriptional activation function of E2 is required for inhibition of the growth of HeLa cells as well as for transcriptional repression of the viral E6/E7 promoter. It had been previously postulated that transcriptional repression of the E6/E7 promoter results from E2 binding its cognate sites proximal to the E6/E7 promoter and displacing other cellular transcriptional factors. In this study, we report a requirement for the transcription activation function for the binding of E2 to transcriptionally active templates.