This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hsu, C.-Y.
Right arrow Articles by Bonne-Andrea, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsu, C.-Y.
Right arrow Articles by Bonne-Andrea, C.

 Previous Article  |  Next Article 

Journal of Virology, January 2007, p. 384-394, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01170-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Nucleocytoplasmic Shuttling of Bovine Papillomavirus E1 Helicase Downregulates Viral DNA Replication in S Phase{triangledown}

Chiung-Yueh Hsu,{dagger} Francisca Mechali, and Catherine Bonne-Andrea*

Centre de Recherches de Biochimie Macromoléculaire, CNRS, FRE 2593, IFR122, 1919 Route de Mende, 34293 Montpellier Cedex 5, France

Received 6 June 2006/ Accepted 5 October 2006

The papillomavirus E1 protein is essential for the initiation of viral replication. We previously showed that the bovine papillomavirus E1 protein is unstable and becomes resistant to ubiquitin-mediated degradation when tightly bound to cyclin E-cyclin-dependent kinase 2 (Cdk2) before the start of DNA synthesis. However, neither the protection nor the targeted degradation of E1 appears to depend on its phosphorylation by Cdk. Here, we report that Cdk phosphorylation of E1 is also not a prerequisite for the initiation of viral DNA replication either in vitro or in vivo. Nevertheless, we found that phosphorylation of one Cdk site, Ser283, abrogates E1 replicative activity only in a cellular context. We show that this site-specific phosphorylation of E1 drives its export from the nucleus and promotes its continuous nucleocytoplasmic shuttling. In addition, we find that E1 shuttling occurs in S phase, when cyclin A-Cdk2 is activated. E1 interacts with the active cyclin A-Cdk2 complex and is phosphorylated on Ser283 by this kinase. These data suggest that the phosphorylation of E1 on Ser283 is a negative regulatory event that is involved in preventing the amplification of viral DNA during S phase. This finding reveals a novel facet of E1 regulation that could account for the variations of the viral replication capacity during different cell cycle phases, as well as in different stages of the viral cycle.

* Corresponding author. Mailing address: Centre de Recherches de Biochimie Macromoléculaire, CNRS, FRE 2593, IFR122, 1919 Route de Mende, 34 293 Montpellier Cedex 5, France. Phone: 33 4 67 61 33 32. Fax: 33 4 67 52 15 59. E-mail: catherine.bonne-andrea{at}crbm.cnrs.fr.

{triangledown} Published ahead of print on 11 October 2006.

{dagger} Present address: Institute of Molecular Biology, Academia Sinica, 128 Academia Road, Nankang, Taipei 11529, Taiwan.

Journal of Virology, January 2007, p. 384-394, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01170-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cote-Martin, A., Moody, C., Fradet-Turcotte, A., D'Abramo, C. M., Lehoux, M., Joubert, S., Poirier, G. G., Coulombe, B., Laimins, L. A., Archambault, J. (2008). Human Papillomavirus E1 Helicase Interacts with the WD Repeat Protein p80 To Promote Maintenance of the Viral Genome in Keratinocytes. J. Virol. 82: 1271-1283 [Abstract] [Full Text]  
  • Yu, J.-H., Lin, B. Y., Deng, W., Broker, T. R., Chow, L. T. (2007). Mitogen-Activated Protein Kinases Activate the Nuclear Localization Sequence of Human Papillomavirus Type 11 E1 DNA Helicase To Promote Efficient Nuclear Import. J. Virol. 81: 5066-5078 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»