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Originally published In Press as doi:10.1074/jbc.M106955200 on January 11, 2002

J. Biol. Chem., Vol. 277, Issue 12, 10427-10434, March 22, 2002
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YB-1 Relocates to the Nucleus in Adenovirus-infected Cells and Facilitates Viral Replication by Inducing E2 Gene Expression through the E2 Late Promoter*

Per S. HolmDagger §, Stephan Bergmann||**, Karsten Jürchott||, Hermann Lage§, Karsten Brand||, Axel Ladhoff§, Klaus MantwillDagger , David T. CurielDagger Dagger , Matthias Dobbelstein§§, Manfred Dietel§, Bernd GänsbacherDagger , and Hans-Dieter Royer||¶¶

From the Dagger  Institut für Experimentelle Onkologie und Therapieforschung, Technische Universität München, Klinikum Rechts der Isar, München 81675, Germany, the § Institut für Pathologie, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Berlin 10117, Germany, the || Max-Delbrück Zentrum für Molekulare Medizin, Berlin 13125, Germany, the §§ Institut für Virologie, Philipps-Universität Marburg, Marburg 35037, Germany, the ¶¶ Institut für Transplantationsdiagnostik und Zelltherapeutika and the ** Institut für Humangenetik und Anthropologie, Heinrich-Heine Universität Düsseldorf, Düsseldorf 40225, Germany, and the Dagger Dagger  Gene Therapy Program, University of Alabama at Birmingham, Wallace Tumor Institute, Birmingham, Alabama 352948

The adenovirus early proteins E1A and E1B-55kDa are key regulators of viral DNA replication, and it was thought that targeting of p53 by E1B-55kDa is essential for this process. Here we have identified a previously unrecognized function of E1B for adenovirus replication. We found that E1B-55kDa is involved in targeting the transcription factor YB-1 to the nuclei of adenovirus type 5-infected cells where it is associated with viral inclusion bodies believed to be sites of viral transcription and replication. We show that YB-1 facilitates E2 gene expression through the E2 late promoter thus controlling E2 gene activity at later stages of infection. The role of YB-1 for adenovirus replication was demonstrated with an E1-minus adenovirus vector containing a YB-1 transgene. In infected cells, AdYB-1 efficiently replicated and produced infectious progeny particles. Thus, adenovirus E1B-55kDa protein and the host cell factor YB-1 act jointly to facilitate adenovirus replication in the late phase of infection.

* This work was supported by Grant Ho 1482/2-2 from the Deutsche Forschungsgemeinschaft (to P. S. H.) and by a Berliner Krebsgesellschaft grant (to H.-D. R.).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.

To whom correspondence should be addressed: Institut für Experimentelle Onkologie und Therapie, Technische Universität München, Klinikum Rechts der Isar, Ismaningerstrasse 22, München 81675, Germany. Tel.: 49-89-4140-4452; Fax: 49-89-4140-4476; E-mail: per.s.holm@lrz.tum.de.

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


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