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HPV 5 and 8 E6 expression reduces ATM protein levels and attenuates LINE-1 retrotransposition

Nicholas A Wallace1, Stephen L Gasior, Zachary J Faber

  • 1Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

Virology
|May 28, 2013
PubMed

Insights

Certain beta human papillomaviruses (β-HPVs) reduce ATM levels, inhibiting LINE-1 retrotransposition by degrading p300. This impacts DNA damage signaling pathways.

Area of Science:

  • Molecular Biology
  • Virology
  • Cancer Research

Background:

  • Beta human papillomaviruses (β-HPVs) E6 proteins disrupt p53 signaling.
  • β-HPV 5 and 8 E6 diminish levels of ATR and p300, key p53 modifying enzymes.

Purpose of the Study:

  • To investigate the effect of β-HPV 5 and 8 E6 on ATM levels and LINE-1 retrotransposition.
  • To determine the role of p300 degradation in ATM reduction and LINE-1 restriction by β-HPV 8 E6.

Main Methods:

  • Assessed the impact of β-HPV 5 and 8 E6 on ATM protein levels.
  • Investigated the effect on LINE-1 retrotransposition.
  • Utilized inhibitors and dominant-negative mutants to confirm ATM's role and the dependency on p300 degradation.

Main Results:

  • β-HPV 5 and 8 E6 reduce ATM levels, consequently restricting LINE-1 retrotransposition.
  • ATM reduction and LINE-1 restriction by β-HPV 8 E6 depend on p300 binding and degradation.
  • ATM is essential for LINE-1 retrotransposition; ATM deficiency does not alter LINE-1 expression sensitivity or DSB formation.

Conclusions:

  • Some β-HPVs broadly impact DNA damage signaling.
  • These β-HPVs promote p300 degradation, affecting ATM levels and LINE-1 retrotransposition.

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