Modulation of bovine papillomavirus DNA replication by phosphorylation of the viral E1 protein.
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.
Zanardi
T A
TA
Department of Biochemistry and Biophysics, Texas A&M University, College Station 77843-2128, USA.
Stanley
C M
CM
Saville
B M
BM
Spacek
S M
SM
Lentz
M R
MR
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
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