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Journal of Virology, June 2006, p. 5261-5272, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02682-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Regulation of the EBNA1 Epstein-Barr Virus Protein by Serine Phosphorylation and Arginine Methylation

Kathy Shire, Priya Kapoor, Ke Jiang, Margaret Ng Thow Hing, Nirojini Sivachandran, Tin Nguyen, and Lori Frappier*

Department of Medical Genetics and Microbiology, University of Toronto, 1 Kings College Circle, Toronto, Canada M5S 1A8

Received 21 December 2005/ Accepted 13 March 2006

The Epstein-Barr virus (EBV) EBNA1 protein is important for the replication and mitotic segregation of EBV genomes in latently infected cells and also activates the transcription of some of the viral latency genes. A Gly-Arg-rich region between amino acids 325 and 376 is required for both the segregation and transcriptional activation functions of EBNA1. Here we show that this region is modified by both arginine methylation and serine phosphorylation. Mutagenesis of the four potentially phosphorylated serines in this region indicated that phosphorylation of multiple serines contributes to the efficient segregation of EBV-based plasmids by EBNA1, at least in part by increasing EBNA1 binding to hEBP2. EBNA1 was also found to bind the arginine methyltransferases PRMT1 and PRMT5. Multiple arginines in the 325-376 region were methylated in vitro by PRMT1 and PRMT5, as was an N-terminal Gly-Arg-rich region between amino acids 41 and 50. EBNA1 was also shown to be methylated in vivo, predominantly in the 325-376 region. Treatment of cells with a methylation inhibitor or down-regulation of PRMT1 altered EBNA1 localization, resulting in the formation of EBNA1 rings around the nucleoli. The results indicate that EBNA1 function is influenced by both serine phosphorylation and arginine methylation.

* Corresponding author. Mailing address: Department of Medical Genetics and Microbiology, University of Toronto, 1 Kings College Circle, Toronto, Canada M5S 1A8. Phone: (416) 946-3501. Fax: (416) 978-6885. E-mail: lori.frappier{at}utoronto.ca.

Journal of Virology, June 2006, p. 5261-5272, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02682-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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