Repression of the human papillomavirus type 18 enhancer by the cellular transcription factor Oct-1.
The role of cellular factors involved in the transcriptional regulation of the cancer-associated human papillomavirus type 18 (HPV18) is yet poorly understood. The presence of an Oct-1-binding site within the HPV18 upstream regulatory region led us to investigate the influence of Oct-1 on viral transcription. Cotransfection of Oct-1 expression plasmids together with luciferase reporter constructs containing HPV18 regulatory sequences indicated that Oct-1 can transcriptionally repress the HPV18 upstream regulatory region. In contrast, heterologous control regions were not affected by Oct-1. HPV18 cis elements that can be repressed by Oct-1 mapped to a 135-bp subregion of the viral constitutive enhancer. Analysis of an Oct-1 mutant defective in DNA binding suggested that HPV18 down-modulation does not require direct binding of Oct-1 to DNA. These results make Oct-1 a candidate factor involved in the intracellular surveillance of HPV18 transcription and support the notion of a host cell mechanism that can specifically repress HPV E6-E7 transforming gene expression.
Hoppe-Seyler
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F
Institut für Virusforschung, Deutsches Krebforschungszentrum, Heidelberg, Germany.
Butz
K
K
zur Hausen
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H
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D005809:Genes, Regulator; D006367:HeLa Cells / Q000378:metabolism; D051863:Host Cell Factor C1; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050811:Octamer Transcription Factor-1; D027383:Papillomaviridae / Q000235:genetics*; D010957:Plasmids; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D014157:Transcription Factors; D008156:Luciferases