title: HPV E7 viral oncoprotein disrupts transcriptional regulation of L1Md retrotransposon.
abstract: Murine L1Md-A5 retrotransposon is a redox-inducible element regulated by Nrf-2/JunD and E2F/Rb-binding sites within its promoter (5'-UTR). Because the human papillomavirus (HPV) oncoprotein E7 interacts with retinoblastoma (pRb) and members of the AP1 family, studies were conducted to examine functional interactions between HPV E7, pRb, and histone deacetylase 2 (HDAC2) in the regulation of L1Md-A5. Using a transient heterologous transcription system we found that HPV E7 alone, or in combination with HDAC2, disrupted pRb-mediated L1MdA-5 transactivation. HPV E7 also ablated the transcriptional response of L1Md-A5 to genotoxic stress, but did not interfere with basal activity. We conclude that HPV E7 associates with proteins involved in the assembly of macromolecular complexes that regulate antioxidant and E2F/Rb sites within L1MdA-5 to regulate biological activity.
authors.affiliation: Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Diego E
authors.initials: DE
authors.lastname: Montoya-Durango
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Ramos
mesh_terms: D052685:Alphapapillomavirus / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells / Q000187:drug effects; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D018626:Retroelements
chemical_list: D002273:Carcinogens; D050684:E2F Transcription Factors; D009856:Oncogene Proteins, Viral; D016160:Retinoblastoma Protein; D018626:Retroelements; D001564:Benzo(a)pyrene; D008156:Luciferases; D056464:Histone Deacetylase 2