title: The Papillomavirus E2 protein binds to and synergizes with C/EBP factors involved in keratinocyte differentiation.
abstract: 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/EBPalpha and -beta 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/EBPbeta sites and the C/EBPalpha-responsive proximal promoter of the involucrin gene, which is naturally expressed in differentiating keratinocytes. C/EBPalpha or -beta 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/EBPbeta. 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.
authors.affiliation: Institute of Virology, University of Cologne, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hadaschik
authors.forename: Korinna
authors.initials: K
authors.lastname: Hinterkeuser
authors.forename: Monika
authors.initials: M
authors.lastname: Oldak
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Pfister
authors.forename: Sigrun
authors.initials: S
authors.lastname: Smola-Hess
mesh_terms: D000818:Animals; D001665:Binding Sites; D052688:Bovine papillomavirus 1 / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002417:Cattle; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D027383:Papillomaviridae / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011498:Protein Precursors; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D011498:Protein Precursors; D014764:Viral Proteins; C032253:involucrin