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Content Provider | Directory of Open Access Journals (DOAJ) |
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Author | Zarina J. D'Costa Carol Jolly Elliot J. Androphy Andrew Mercer Charles M. Matthews Merilyn H. Hibma |
Abstract | There is increasing evidence supporting DNA virus regulation of the cell adhesion and tumour suppressor protein, E-cadherin. We previously reported that loss of E-cadherin in human papillomavirus (HPV) type 16-infected epidermis is contributed to by the major viral proto-oncogene E6 and is associated with reduced Langerhans cells density, potentially regulating the immune response. The focus of this study is determining how the HPV16 E6 protein mediates E-cadherin repression. We found that the E-cadherin promoter is repressed in cells expressing E6, resulting in fewer E-cadherin transcripts. On exploring the mechanism for this, repression by increased histone deacetylase activity or by increased binding of trans-repressors to the E-cadherin promoter Epal element was discounted. In contrast, DNA methyltransferase (DNMT) activity was increased in E6 expressing cells. Upon inhibiting DNMT activity using 5-Aza-2'-deoxycytidine, E-cadherin transcription was restored in the presence of HPV16 E6. The E-cadherin promoter was not directly methylated, however a mutational analysis showed general promoter repression and reduced binding of the transactivators Sp1 and AML1 and the repressor Slug. Expression of E7 with E6 resulted in a further reduction in surface E-cadherin levels. This is the first report of HPV16 E6-mediated transcriptional repression of this adhesion molecule and tumour suppressor protein. |
e-ISSN | 19326203 |
DOI | 10.1371/journal.pone.0048954 |
Journal | PLoS ONE |
Issue Number | 11 |
Volume Number | 7 |
Language | English |
Publisher | Public Library of Science (PLoS) |
Publisher Date | 2012-01-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Medicine Science |
Content Type | Text |
Resource Type | Article |
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