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dc.contributor.authorVieira, Valdimara C.en_US
dc.contributor.authorLeonard, Brandonen_US
dc.contributor.authorWhite, Elizabeth A.en_US
dc.contributor.authorStarrett, Gabriel J.en_US
dc.contributor.authorTemiz, Nuri A.en_US
dc.contributor.authorLorenz, Laurel D.en_US
dc.contributor.authorLee, Denisen_US
dc.contributor.authorSoares, Marcelo A.en_US
dc.contributor.authorLambert, Paul F.en_US
dc.contributor.authorHowley, Peter M.en_US
dc.contributor.authorHarris, Reuben S.en_US
dc.date.accessioned2015-01-05T18:28:18Z
dc.date.issued2014en_US
dc.identifier.citationVieira, V. C., B. Leonard, E. A. White, G. J. Starrett, N. A. Temiz, L. D. Lorenz, D. Lee, et al. 2014. “Human Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3B.” mBio 5 (6): e02234-14. doi:10.1128/mBio.02234-14. http://dx.doi.org/10.1128/mBio.02234-14.en
dc.identifier.issn2150-7511en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13581233
dc.description.abstractABSTRACT Several recent studies have converged upon the innate immune DNA cytosine deaminase APOBEC3B (A3B) as a significant source of genomic uracil lesions and mutagenesis in multiple human cancers, including those of the breast, head/neck, cervix, bladder, lung, ovary, and other tissues. A3B is upregulated in these tumor types relative to normal tissues, but the mechanism is unclear. Because A3B also has antiviral activity in multiple systems and is a member of the broader innate immune response, we tested the hypothesis that human papillomavirus (HPV) infection causes A3B upregulation. We found that A3B mRNA expression and enzymatic activity were upregulated following transfection of a high-risk HPV genome and that this effect was abrogated by inactivation of E6. Transduction experiments showed that the E6 oncoprotein alone was sufficient to cause A3B upregulation, and a panel of high-risk E6 proteins triggered higher A3B levels than did a panel of low-risk or noncancer E6 proteins. Knockdown experiments in HPV-positive cell lines showed that endogenous E6 is required for A3B upregulation. Analyses of publicly available head/neck cancer data further support this relationship, as A3B levels are higher in HPV-positive cancers than in HPV-negative cancers. Taken together with the established role for high-risk E6 in functional inactivation of TP53 and published positive correlations in breast cancer between A3B upregulation and genetic inactivation of TP53, our studies suggest a model in which high-risk HPV E6, possibly through functional inactivation of TP53, causes derepression of A3B gene transcription. This would lead to a mutator phenotype that explains the observed cytosine mutation biases in HPV-positive head/neck and cervical cancers.en
dc.language.isoen_USen
dc.publisherAmerican Society of Microbiologyen
dc.relation.isversionofdoi:10.1128/mBio.02234-14en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278539/pdf/en
dash.licenseLAAen_US
dc.titleHuman Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3Ben
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalmBioen
dash.depositing.authorWhite, Elizabeth A.en_US
dc.date.available2015-01-05T18:28:18Z
dc.identifier.doi10.1128/mBio.02234-14*
dash.authorsorderedfalse
dash.contributor.affiliatedWhite, Elizabeth A.
dash.contributor.affiliatedHowley, Peter


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