The human papillomavirus 16 E2 protein is stabilised in S phase.
The human papillomavirus 16 E2 protein regulates transcription from, and replication of, the viral genome and is also required for segregation of the viral genome via interaction with mitotic bodies. To regulate DNA replication E2 interacts with sequences around the origin of replication and recruits the viral helicase E1 via a protein-protein interaction, which then initiates viral genome replication. The replication role of E2 must originally function in a host cell S phase. In this report, we demonstrate that E2 is stabilised in the S phase of the cell cycle and that this stabilisation is accompanied by an increase in phosphorylation of the protein. This increased phosphorylation and stability are likely required for optimum viral DNA replication and therefore identification of the enzymes involved in regulating these properties of E2 will provide targets for therapeutic intervention in the viral life cycle. Preliminary studies have identified E2 as a Cdk2 substrate demonstrating this enzyme as a candidate kinase for mediating the in vivo phosphorylation of HPV16 E2.
Institute of Comparative Medicine, University of Glasgow Faculty of Veterinary Medicine, Glasgow, G61 1QH, UK.
Cecilia
C
Johansson
Sheila V
SV
Graham
Edward S
ES
Dornan
Iain M
IM
Morgan
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D013379:Substrate Specificity
D002843:Chromatin; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2