Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity

Leiping Fu, Koenraad van Doorslaer, Zigui Chen, Tutik Ristriani, Murielle Masson, Gilles Travé, Robert D. Burk

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background: Human Papillomavirus (HPV) E6 induced p53 degradation is thought to be an essential activity by which highrisk human Alphapapillomaviruses (alpha-HPVs) contribute to cervical cancer development. However, most of our understanding is derived from the comparison of HPV16 and HPV11. These two viruses are relatively distinct viruses, making the extrapolation of these results difficult. In the present study, we expand the tested strains (types) to include members of all known HPV species groups within the Alphapapillomavirus genus. Principal Findings: We report the biochemical activity of E6 proteins from 27 HPV types representing all alpha-HPV species groups to degrade p53 in human cells. Expression of E6 from all HPV types epidemiologically classified as group 1 carcinogens significantly reduced p53 levels. However, several types not associated with cancer (e.g., HPV53, HPV70 and HPV71) were equally active in degrading p53. HPV types within species groups alpha 5, 6, 7, 9 and 11 share a most recent common ancestor (MRCA) and all contain E6 ORFs that degrade p53. A unique exception, HPV71 E6 ORF that degraded p53 was outside this clade and is one of the most prevalent HPV types infecting the cervix in a population-based study of 10,000 women. Alignment of E6 ORFs identified an amino acid site that was highly correlated with the biochemical ability to degrade p53. Alteration of this amino acid in HPV71 E6 abrogated its ability to degrade p53, while alteration of this site in HPV71-related HPV90 and HPV106 E6s enhanced their capacity to degrade p53. Conclusions: These data suggest that the alpha-HPV E6 proteins' ability to degrade p53 is an evolved phenotype inherited from a most recent common ancestor of the high-risk species that does not always segregate with carcinogenicity. In addition, we identified an amino-acid residue strongly correlated with viral p53 degrading potential.

Original languageEnglish (US)
Article numbere12816
Pages (from-to)1-8
Number of pages8
JournalPLoS One
Volume5
Issue number9
DOIs
StatePublished - 2010

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Alphapapillomavirus
carcinogenicity
Phylogeny
Papillomaviridae
Viruses
Amino Acids
Degradation
degradation
phylogeny
Proteins
proteins
Extrapolation
Carcinogens
open reading frames
Open Reading Frames
Cells
Human papillomavirus 2
amino acids
ancestry
viruses

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity. / Fu, Leiping; van Doorslaer, Koenraad; Chen, Zigui; Ristriani, Tutik; Masson, Murielle; Travé, Gilles; Burk, Robert D.

In: PLoS One, Vol. 5, No. 9, e12816, 2010, p. 1-8.

Research output: Contribution to journalArticle

Fu, Leiping ; van Doorslaer, Koenraad ; Chen, Zigui ; Ristriani, Tutik ; Masson, Murielle ; Travé, Gilles ; Burk, Robert D. / Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity. In: PLoS One. 2010 ; Vol. 5, No. 9. pp. 1-8.
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