The Papillomavirus E2 protein binds to and synergizes with C/EBP factors involved in keratinocyte differentiation.

  • Hadaschik D
  • Hinterkeuser K
  • Oldak M
 et al. 
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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.

Author-supplied keywords

  • Animals
  • Binding Sites
  • Bovine papillomavirus 1
  • Bovine papillomavirus 1: metabolism
  • CCAAT-Enhancer-Binding Proteins
  • CCAAT-Enhancer-Binding Proteins: metabolism
  • Cattle
  • Cell Differentiation
  • Cell Line
  • DNA-Binding Proteins
  • DNA-Binding Proteins: metabolism
  • Gene Expression Regulation
  • Humans
  • Keratinocytes
  • Keratinocytes: cytology
  • Papillomaviridae
  • Papillomaviridae: metabolism
  • Promoter Regions, Genetic
  • Protein Precursors
  • Transcriptional Activation
  • Viral Proteins
  • Viral Proteins: metabolism

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  • Dirk Hadaschik

  • Korinna Hinterkeuser

  • Monika Oldak

  • Herbert J Pfister

  • Sigrun Smola-Hess

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