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Cross-talk between phosphorylation and SUMOylation regulates transforming activities of an adenoviral oncoprotein

Oncogene volume 32, pages 1626–1637 (2013)Cite this article

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Abstract

Since the discovery of post-translational modification (PTM) by the small ubiquitin-related modifiers (SUMOs), a multitude of proteins have been described to be reversibly modified, resulting in the alteration of several cellular pathways. Interestingly, various pathogens gain access to this modification system, although the molecular mechanisms and functional consequences are barely understood. We show here that the adenoviral oncoprotein E1B-55K is a substrate of the SUMO conjugation system, which is directly linked to its C-terminal phosphorylation. This regulative connection is indispensable for modulation of the tumor suppressor p53/chromatin-remodeling factor Daxx by E1B-55K and, consequently, its oncogenic potential in primary mammalian cells. In virus infection, E1B-55K PTMs are necessary for localization to viral transcription/replication sites. Furthermore, we identify the E2 enzyme Ubc9 as an interaction partner of E1B-55K, providing a possible molecular explanation for SUMO-dependent modulation of cellular target proteins. In conclusion, these results for the first time provide evidence how E1B-55K PTMs are regulated and subsequently facilitate exploitation of the host cell SUMOylation machinery.

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Acknowledgements

We apologize for all the important publications and excellent reviews we could not cite/refer to due to space limitations. The Heinrich–Pette–Institute is supported by the ‘Freie und Hansestadt Hamburg’ and the ‘Bundesministerium für Gesundheit’. TD was supported by a grant from the Wilhelm Sander-Stiftung, Munich, Germany. PEB and PB were supported through grants from the Canadian Institutes of Health Research.

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Authors and Affiliations

  1. Department of Molecular Virology, Heinrich–Pette–Institute—Leibniz-Institute for Experimental Virology, Hamburg, Germany

    P Wimmer, S Schreiner, W Ching, P Groitl, J Berscheminski, H Will & T Dobner

  2. Department of Biochemistry, McGill University, Montreal, Canada

    P Blanchette & P E Branton

  3. Department of Oncology, McGill University, Montreal, Canada

    P E Branton

  4. The Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada

    P E Branton

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  1. P Wimmer
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Wimmer, P., Blanchette, P., Schreiner, S. et al. Cross-talk between phosphorylation and SUMOylation regulates transforming activities of an adenoviral oncoprotein. Oncogene 32, 1626–1637 (2013). https://doi.org/10.1038/onc.2012.187

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