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Originally published In Press as doi:10.1074/jbc.M111872200 on March 23, 2002

J. Biol. Chem., Vol. 277, Issue 23, 21050-21060, June 7, 2002
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Phosphorylation of Varicella-Zoster Virus IE63 Protein by Casein Kinases Influences Its Cellular Localization and Gene Regulation Activity*

Sébastien BontemsDagger , Emmanuel Di Valentin§, Laurence Baudoux, Bernard Rentier, Catherine Sadzot-Delvaux, and Jacques Piette

From the Laboratory of Virology and Immunology, University of Liège, B-4000 Liège, Belgium

During the early phase of varicella-zoster virus (VZV) infection, Immediate Early protein 63 (IE63) is expressed rapidly and abundantly in the nucleus, while during latency, this protein is confined mostly to the cytoplasm. Because phosphorylation is known to regulate many cellular events, we investigated the importance of this modification on the cellular localization of IE63 and on its regulatory properties. We demonstrate here that cellular casein kinases I and II are implicated in the in vitro and in vivo phosphorylation of IE63. A mutational approach also indicated that phosphorylation of the protein is important for its correct cellular localization in a cell type-dependent fashion. Using an activity test, we demonstrated that IE63 was able to repress the gene expression driven by two VZV promoters and that phosphorylation of the protein was required for its full repressive properties. Finally, we showed that IE63 was capable of exerting its repressive activity in the cytoplasm, as well as in the nucleus, suggesting a regulation at the transcriptional and/or post-transcriptional level.

* This work was supported in part by a grant from the Belgian National Fund for Scientific Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Supported by Televie.

§ Supported by Fonds pour la Recherche en Industrie et Agriculture.

Research director at the Belgian National Fund for Scientific Research. To whom correspondence should be addressed: Laboratory of Virology and Immunology, Institute of Pathology B23, University of Liège, B-4000 Liège, Belgium. Tel.: 32-4-366-2442; Fax: 32-4-366-9933; E-mail: jpiette@ulg.ac.be.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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