Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation

SA Southern, MH Lewis, Charles Simon Herrington

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

We have demonstrated previously that high-risk human papillomaviruses (HPVs) induce tetrasomy in low-grade squamous intraelpithelial lesions of the cervix. In this study we show that the E6 and E7 genes of high-risk HPV-16, but not those of low-risk HPV-6, are independently able to induce tetrasomy when constitutively expressed in proliferating monolayer cultures of primary human keratinocytes. Of seven HPV-16 E7 mutants analysed (H2P, Delta6-10, Delta21-24, C24G, S31G/S32G, A50S and S711), five were severely impaired in their ability to induce tetrasomy in monolayer and raft culture. Only mutant C24G induced tetrasomy to levels comparable with wild-type E7 in monolayer and raft culture. This mutant shows strongly reduced binding to the retinoblastoma gene product pRb. The casein kinase II phosphorylation defective mutant S31G/S32G induced tetrasomy to levels comparable with wildtype E7 in raft culture, but not in monolayer culture, and induction of tetrasomy did not correlate with raft morphology. These results indicate that pRb protein binding is not required for HPV-16 E7 associated tetrasomy and that tetrasomy is not directly related to the ability of this protein to disrupt keratinocyte differentiation. (C) 2004 Cancer Research UK.

Original languageEnglish
Pages (from-to)1949-1954
Number of pages6
JournalBritish Journal of Cancer
Volume90
Issue number10
DOIs
Publication statusPublished - 17 May 2004

Keywords

  • human papillomavirus
  • keratinocyte
  • tetrasomy
  • SQUAMOUS INTRAEPITHELIAL LESIONS
  • RETINOBLASTOMA TUMOR-SUPPRESSOR
  • HUMAN EPITHELIAL-CELLS
  • DNA-REPLICATION
  • GENE-EXPRESSION
  • TRANSFORMATION
  • KERATINOCYTES
  • ONCOPROTEIN
  • ABROGATION
  • SUFFICIENT

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