Document Detail

Human papillomavirus type 16 E6 protein transcriptionally modulates fibronectin gene expression by induction of protein complexes binding to the cyclic AMP response element.
MedLine Citation:
PMID:  9151819     Owner:  NLM     Status:  MEDLINE    
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.
Y Shino; H Shirasawa; T Kinoshita; B Simizu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of virology     Volume:  71     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-06-09     Completed Date:  1997-06-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4310-8     Citation Subset:  IM    
Department of Microbiology, School of Medicine, Chiba University, Chuo-ku, Japan.
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MeSH Terms
Adenovirus E1A Proteins / physiology
Binding Sites
Cell Line
Cyclic AMP / physiology
DNA-Binding Proteins / genetics*
Fibronectins / genetics*
Gene Expression Regulation, Viral*
Oncogene Proteins, Viral / genetics*
Promoter Regions, Genetic*
Repressor Proteins*
Transcription Factor AP-1 / metabolism
Transcription, Genetic
Transcriptional Activation
Reg. No./Substance:
0/Adenovirus E1A Proteins; 0/DNA-Binding Proteins; 0/E6 protein, Human papillomavirus type 16; 0/Fibronectins; 0/Oncogene Proteins, Viral; 0/Repressor Proteins; 0/Transcription Factor AP-1; 60-92-4/Cyclic AMP

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