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Journal of Virology, April 2003, p. 5008-5013, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.5008-5013.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus Nuclear Antigen 2 Binds via Its Methylated Arginine-Glycine Repeat to the Survival Motor Neuron Protein

Stephanie Barth,1 Michael Liss,2 Marc D. Voss,1 Thomas Dobner,2 Utz Fischer,3 Gunter Meister,3 and Friedrich A. Grässer1*

Institut für Medizinische Mikrobiologie und Hygiene, Abteilung Virologie, Universitätskliniken des Saarlandes, 66421 Homburg/Saar,1 Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum, 93053 Regensburg,2 Max Planck Institut für Biochemie, 82152 Martinsried/Munich, Germany3

Received 19 September 2002/ Accepted 22 January 2003

Here we provide evidence that EBNA2 is methylated in vivo and that methylation of EBNA2 is a prerequisite for binding to SMN. We present SMN as a novel binding partner of EBNA2 by showing that EBNA2 colocalizes with SMN in nuclear gems and that both proteins can be coimmunoprecipitated from cellular extract. Furthermore, in vitro methylation of either wild-type EBNA2 or a glutathione S-transferase-EBNA2 fusion protein encompassing the arginine-glycine (RG) repeat element is necessary for in vitro binding to the Tudor domain of SMN. The recently shown functional cooperation of SMN and EBNA2 in transcriptional activation and the previous observation of a severely reduced transformation potential yet strongly enhanced transcriptional activity of an EBNA2 mutant lacking the RG repeat indicate that binding of SMN to EBNA2 is a critical step in B-cell transformation by Epstein-Barr virus.

* Corresponding author. Mailing address: Institut für Mikrobiologie und Hygiene Abteilung Virologie, Haus 47, Universitätskliniken, 66421 Homburg/Saar, Germany. Phone: 49-6841-162 3983. Fax: 49-6841-162 3980. E-mail: graesser{at}uniklinik-saarland.de.

Journal of Virology, April 2003, p. 5008-5013, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.5008-5013.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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