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. 1997 Jun;71(6):4310–4318. doi: 10.1128/jvi.71.6.4310-4318.1997

Human papillomavirus type 16 E6 protein transcriptionally modulates fibronectin gene expression by induction of protein complexes binding to the cyclic AMP response element.

Y Shino 1, H Shirasawa 1, T Kinoshita 1, B Simizu 1
PMCID: PMC191647  PMID: 9151819

Abstract

Although human papillomavirus type 16 (HPV16) E6 protein has a transcription-modulatory activity for a wide variety of viral promoters, a cellular target for this activity of E6 has not yet been identified. In this study, using differential hybridization, we identified a mouse fibronectin (FN) gene as a putative cellular target whose expression is up-regulated by E6. Chloramphenicol acetyltransferase (CAT) assays with mouse and rat FN promoter-CAT fusion constructs indicated that HPV16 E6 transactivates the FN promoters in a p53-independent manner. Deletion and site-specific mutation analyses revealed that transactivation by HPV16 E6 depends upon a cyclic AMP response element (CRE) located at -160 relative to the start site of transcription. Gel retardation assays demonstrated that nuclear extracts from the HPV16 E6-expressing cells, compared to those from parental 10T1/2 cells, have increased binding activity to the CRE. Antibodies against c-Jun and ATF-2 disrupted this binding activity. These data indicate that HPV16 E6 transcriptionally modulates FN gene expression via the CRE by inducing the binding of the protein complexes, probably including c-Jun and ATF-2, to the CRE.

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Selected References

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