Phosphorylation of varicella-zoster virus IE63 protein by casein kinases influences its cellular localization and gene regulation activity.

The Journal of Biological Chemistry
Sebastien BontemsJ Piette

Abstract

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.

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Citations

Sep 15, 2007·Journal of Virology·Nadia El MjiyadCatherine Sadzot-Delvaux
Dec 23, 2004·Journal of Virology·David J DavidoPriscilla A Schaffer
Feb 28, 2006·Journal of Virology·Jeremy O JonesAnn M Arvin
Feb 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Xavier DanielElaine M Tobin
Apr 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Leigh ZerboniAnn M Arvin
Feb 11, 2014·Nature Reviews. Microbiology·Leigh ZerboniAnn M Arvin
Nov 16, 2010·Virus Research·Jennifer M FolsterD Scott Schmid
Jun 19, 2004·The International Journal of Biochemistry & Cell Biology·Bernard LakayeLucien Bettendorff
Jan 22, 2010·The Journal of General Virology·Niklaus H MuellerRandall J Cohrs

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