title: Regulation of the human papillomavirus type 16 late promoter by E7 and the cell cycle.
abstract: Human papillomaviruses (HPVs) are the causative agents of cervical and other cancers. The oncoprotein E7 activates the cell cycle and makes possible replication of the viral genome in differentiating epithelia. The HPV16 late promoter is activated upon cellular differentiation and regulates late gene expression. We investigated the effect of E7 on the late promoter and found that E7 was able to activate the promoter. In contrast, the other known viral transcriptional regulator, E2, had no effect on the late promoter. Promoter activation by E7 occurred despite inhibition of promoter activity by factors involved in the cell cycle, such as cyclin dependent kinases and E2F transcription factors, and by the ability of E7 to disrupt several aspects of cellular differentiation. These results suggest a new role for E7 in the context of the viral life cycle and shed light on the complex regulation of viral gene expression in infected, differentiating epithelia.
authors.affiliation: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. jbodil@lsuhsc.edu
authors.forename: Jason M
authors.initials: JM
authors.lastname: Bodily
authors.forename: Christine
authors.initials: C
authors.lastname: Hennigan
authors.forename: Gary A
authors.initials: GA
authors.lastname: Wrobel
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Rodriguez
mesh_terms: D002453:Cell Cycle; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16