title: Human papillomavirus type 16 E6 protein transcriptionally modulates fibronectin gene expression by induction of protein complexes binding to the cyclic AMP response element.
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.
authors.affiliation: Department of Microbiology, School of Medicine, Chiba University, Chuo-ku, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shino
authors.forename: H
authors.initials: H
authors.lastname: Shirasawa
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: B
authors.initials: B
authors.lastname: Simizu
mesh_terms: D017500:Adenovirus E1A Proteins / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005353:Fibronectins / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D012097:Repressor Proteins; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D005353:Fibronectins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D000242:Cyclic AMP