HPV 5 and 8 E6 expression reduces ATM protein levels and attenuates LINE-1 retrotransposition
| Autor: | Nicholas A. Wallace, Stephen L. Gasior, Prescott L. Deininger, Zachary J Faber, Heather L. Howie, Denise A. Galloway |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
DNA damage
Proteolysis Mutant Cell Cycle Proteins P300-CBP Transcription Factors Ataxia Telangiectasia Mutated Proteins Biology Protein Serine-Threonine Kinases DNA-binding protein Article 03 medical and health sciences LINE-1 0302 clinical medicine Virology medicine DNA damage repair Betapapillomavirus Humans p300-CBP Transcription Factors 030304 developmental biology chemistry.chemical_classification Recombination Genetic 0303 health sciences medicine.diagnostic_test Tumor Suppressor Proteins Beta HPV E6 Oncogene Proteins Viral Molecular biology Retrotransposition DNA-Binding Proteins Enzyme Long Interspersed Nucleotide Elements chemistry 030220 oncology & carcinogenesis ATM Steady state (chemistry) HeLa Cells |
| Zdroj: | Virology. 443(1) |
| ISSN: | 1096-0341 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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