The Papillomavirus E2 Protein Binds to and Synergizes with C/EBP Factors Involved in Keratinocyte Differentiation
Autor: | Herbert Pfister, Sigrun Smola-Hess, Dirk Hadaschik, Monika Ołdak, Korinna Hinterkeuser |
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Rok vydání: | 2003 |
Předmět: |
Keratinocytes
Transcriptional Activation viruses Immunology Microbiology Cell Line Viral Proteins In vivo Virology medicine Animals Humans Protein Precursors Binding site Promoter Regions Genetic Papillomaviridae Transcription factor Bovine papillomavirus 1 Bovine papillomavirus chemistry.chemical_classification Binding Sites biology C-terminus Cell Differentiation biology.organism_classification Molecular biology In vitro Virus-Cell Interactions Amino acid DNA-Binding Proteins medicine.anatomical_structure Gene Expression Regulation chemistry Insect Science CCAAT-Enhancer-Binding Proteins Cattle Keratinocyte |
Zdroj: | Journal of Virology. 77:5253-5265 |
ISSN: | 1098-5514 0022-538X |
DOI: | 10.1128/jvi.77.9.5253-5265.2003 |
Popis: | The papillomavirus life cycle is closely linked to the differentiation program of the host keratinocyte. Thus, late gene expression and viral maturation are restricted to terminally differentiated keratinocytes. A variety of cellular transcription factors including those of the C/EBP family are involved in the regulation of keratinocyte differentiation. In this study we show that the papillomavirus transcription factor E2 cooperates with C/EBPα and -β in transcriptional activation. This synergism was independent of an E2 binding site. E2 and C/EBP factors synergistically transactivated a synthetic promoter construct containing classical C/EBPβ sites and the C/EBPα-responsive proximal promoter of the involucrin gene, which is naturally expressed in differentiating keratinocytes. C/EBPα or -β coprecipitated with E2 proteins derived from human papillomavirus type 8 (HPV8), HPV16, HPV18, and bovine papillomavirus type 1 in vitro and in vivo, indicating complex formation by the cellular and viral factors. The interaction domains could be mapped to the C terminus of E2 and amino acids 261 to 302 located within the bZIP motif of C/EBPβ. Our data suggest that E2, via its interaction with C/EBP factors, may contribute to enhancing keratinocyte differentiation, which is suppressed by the viral oncoproteins E6 and E7 in HPV-induced lesions. |
Databáze: | OpenAIRE |
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