title: HPV 5 and 8 E6 expression reduces ATM protein levels and attenuates LINE-1 retrotransposition.
abstract: The expression of the E6 protein from certain members of the HPV genus β (β HPV 5 and 8 E6) can disrupt p53 signaling by diminishing the steady state levels of two p53 modifying enzymes, ATR and p300. Here, we show that β-HPV 5 and 8 E6 are also capable of reducing the steady state levels of another p53 modifying enzyme, ATM, and as a result restrict LINE-1 retrotransposition. Furthermore, we show that the reduction of both ATM and LINE-1 retrotransposition is dependent upon the ability of β-HPV 8 E6 to bind and degrade p300. We use inhibitors and dominant negative mutants to confirm that ATM is needed for efficient LINE-1 retrotransposition. Furthermore, neither sensitivity to LINE-1 expression nor LINE-1 induced DSB formation is altered in an ATM deficient background. Together, these data illustrate the broad impact some β-HPVs have on DNA damage signaling by promoting p300 degradation.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Wallace
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Gasior
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Faber
authors.forename: Heather L
authors.initials: HL
authors.lastname: Howie
authors.forename: Prescott L
authors.initials: PL
authors.lastname: Deininger
authors.forename: Denise A
authors.initials: DA
authors.lastname: Galloway
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D052686:Betapapillomavirus / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D059748:Proteolysis; D011995:Recombination, Genetic; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors*; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors; D000099224:p300-CBP-Associated Factor
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C576324:ATM protein, human