title: Modulation of bovine papillomavirus DNA replication by phosphorylation of the viral E1 protein.
abstract: E1 is the DNA replication origin recognition protein for bovine papillomavirus (BPV), and it carries out enzymatic functions required for initiation of viral DNA replication. Cellular mechanisms likely play a role in regulating BPV DNA replication. We are investigating the role of phosphorylation of E1 on viral replication in vivo and on E1 activity in vitro. Serine 109 is a phosphoacceptor in vivo and is targeted by protein kinase A and protein kinase C in vitro. A viral genome carrying a serine 109 to alanine mutation replicates more efficiently than wild-type in vivo in a transient replication assay. Furthermore, purified mutant protein, while having wild-type levels of ATPase activity, is able to bind more origin-containing DNA than wild-type E1. Phosphorylation therefore appears to play a selective role in modulating a specific E1 function during viral DNA replication.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station 77843-2128, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Zanardi
authors.forename: C M
authors.initials: CM
authors.lastname: Stanley
authors.forename: B M
authors.initials: BM
authors.lastname: Saville
authors.forename: S M
authors.initials: SM
authors.lastname: Spacek
authors.forename: M R
authors.initials: MR
authors.lastname: Lentz
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000409:Alanine; D000818:Animals; D001665:Binding Sites; D052688:Bovine papillomavirus 1 / Q000235:genetics / Q000502:physiology*; D016466:CHO Cells; D002417:Cattle; D002460:Cell Line; D006224:Cricetinae; D004265:DNA Helicases; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016679:Genome, Viral; D018698:Glutamic Acid; D051379:Mice; D016296:Mutagenesis; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D012694:Serine; D018411:Spodoptera / Q000166:cytology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C069814:E1 protein, Bovine papillomavirus; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D018698:Glutamic Acid; D012694:Serine; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D000409:Alanine