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人乳头瘤病毒16型长控制区中的增强子被PEF-1上调,并被Oct-1下调。

The enhancer in the long control region of human papillomavirus type 16 is up-regulated by PEF-1 and down-regulated by Oct-1.

作者信息

Sibbet G J, Cuthill S, Campo M S

机构信息

Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, Scotland.

出版信息

J Virol. 1995 Jul;69(7):4006-11. doi: 10.1128/JVI.69.7.4006-4011.1995.

Abstract

The minimal enhancer in the long control region of human papillomavirus type 16 regulates cell type and constitutive expression from the promoter P97. This region contains at least four DNase I footprints (fp4e, fp5e, fp6e, and fp7e). We have shown that fp5e is crucial to enhancer function and have described an apparently novel factor (PEF-1) binding fp5e (S. Cuthill, G. J. Sibbet, and M. S. Campo, Mol. Carcinog. 8:9-104, 1993). Further analyses reveal that Oct-1 or an Oct-related factor binds fp5e at a site overlapping that of PEF-1. The binding of Oct-1 to fp5e has been demonstrated by electrophoretic mobility shift assays, by oligonucleotide competition studies, and by using an Oct-1-specific anti-POU serum. The location of the Oct-1 site has been confirmed by a panel of mutants across fp5e. Mutations that block PEF-1 binding to fp5e also block enhancer/promoter activity of the long control region, whereas mutations that block Oct-1 binding significantly increase enhancer/promoter activity. Thus, although both PEF-1 and Oct-1 interact with fp5e, they appear to regulate human papillomavirus expression in opposite ways.

摘要

人乳头瘤病毒16型长控制区中的最小增强子调控细胞类型及启动子P97的组成型表达。该区域包含至少四个DNase I足迹(fp4e、fp5e、fp6e和fp7e)。我们已证明fp5e对增强子功能至关重要,并描述了一种明显新颖的因子(PEF-1)与fp5e结合(S. Cuthill、G. J. Sibbet和M. S. Campo,《分子致癌作用》8:9 - 104,1993年)。进一步分析表明,Oct-1或一个Oct相关因子在与PEF-1重叠的位点结合fp5e。通过电泳迁移率变动分析、寡核苷酸竞争研究以及使用Oct-1特异性抗POU血清,已证实Oct-1与fp5e的结合。通过一组跨越fp5e的突变体,已确认Oct-1位点的位置。阻断PEF-1与fp5e结合的突变也会阻断长控制区的增强子/启动子活性,而阻断Oct-1结合的突变则会显著增加增强子/启动子活性。因此,尽管PEF-1和Oct-1都与fp5e相互作用,但它们似乎以相反的方式调控人乳头瘤病毒的表达。

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