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