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  • Original Paper
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The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2

Oncogene volume 19, pages 850–857 (2000)Cite this article

Abstract

The E1B-55K and E4orf6 oncoproteins of adenovirus type 5 are involved in the export of viral mRNAs. Previously, it was suggested that a complex composed of E1B-55K and E4orf6 serves as a nucleocytoplasmic transporter for viral mRNAs in which the E4orf6 protein directs both nuclear import and export. We now demonstrate that the E1B-55K protein itself shuttles efficiently in the absence of E4orf6. In addition, E1B-55K trafficking was independent of the defined shuttle proteins Mdm2 or p53, which interacts with E1B-55K. The identified N-terminal E1B-55K leucine-rich nuclear-export signal (NES) conferred rapid nuclear export even in a heterologous system in contrast to the postulated E4orf6NES. Interestingly, although shuttling was blocked by inhibitors of the CRM1 mediated export pathway, E1B-55K inhibited neither the activity nor the trafficking of the retroviral shuttle proteins HIV-1 Rev and HTLV-1 Rex. In contrast, Rev or Rex blocked the nuclear export of E1B-55K, most likely by competing for essential export factors. Our results provide new insights into the regulation of the adenovirus mRNA export system and the processes of adenovirus mediated transformation.

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Acknowledgements

F Krätzer and O Rosorius contributed equally to the work. We thank Grit Schneider for excellent technical assistance and Bernhard Fleckenstein for continuous support. Purified Ad5 and LMB was kindly provided by Walter Dörfler and the Novartis Research Institute Vienna, respectively. R Stauber is supported by the DKFZ AIDS-Stipendium Programm. This work was supported by the Deutsche Forschungsgemeinschaft (SFB466), the Wilhelm-Sander Stiftung (98.090.1/96.042.2) and the Kalkhof-Rose Stiftung.

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  1. Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Schlossgarten 4, Erlangen, D-91054, Germany

    Friedrich Krätzer, Olaf Rosorius, Peter Heger, Nicole Hirschmann, Joachim Hauber & Roland H Stauber

  2. Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, D-93053, Germany

    Thomas Dobner

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Krätzer, F., Rosorius, O., Heger, P. et al. The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2. Oncogene 19, 850–857 (2000). https://doi.org/10.1038/sj.onc.1203395

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