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Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation

Oncogene volume 29, pages 4693–4704 (2010)Cite this article

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Abstract

Hub proteins have central roles in regulating cellular processes. By targeting a single cellular hub, a viral oncogene may gain control over an entire module in the cellular interaction network that is potentially comprised of hundreds of proteins. The adenovirus E1A oncoprotein is a viral hub that interacts with many cellular hub proteins by short linear motifs/molecular recognition features (MoRFs). These interactions transform the architecture of the cellular protein interaction network and virtually reprogram the cell. To identify additional MoRFs within E1A, we screened portions of E1A for their ability to activate yeast pseudohyphal growth or differentiation. This identified a novel functional region within E1A conserved region 2 comprised of the sequence EVIDLT. This MoRF is necessary and sufficient to bind the N-terminal region of the SUMO conjugase UBC9, which also interacts with SUMO noncovalently and is involved in polySUMOylation. Our results suggest that E1A interferes with polySUMOylation, but not with monoSUMOylation. These data provide the first insight into the consequences of the interaction of E1A with UBC9, which was initially described in 1996. We further demonstrate that polySUMOylation regulates pseudohyphal growth and promyelocytic leukemia body reorganization by E1A. In conclusion, the interaction of the E1A oncogene with UBC9 mimics the normal binding between SUMO and UBC9 and represents a novel mechanism to modulate polySUMOylation.

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Acknowledgements

This work was supported by a grant from the Canadian Institutes of Health Research to JSM (MOP-75647). AFY and PP were supported by CIHR Strategic Training Program in Cancer Research and Technology Transfer awards. GJF and JNA held OGS and OGSST awards. We thank Drs C Brandl, R Hay, J Taylor, K Uzunova, J Dohmen, A Strunnikov, G Fink, E Yeh and O Janne for generously providing reagents essential for this study.

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  1. G J Fonseca and P Pelka: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada

    A F Yousef, G J Fonseca, J N G Ablack, C Walsh & J S Mymryk

  2. Department of Oncology, London Regional Cancer Centre, The University of Western Ontario, London, Ontario, Canada

    P Pelka, F A Dick & J S Mymryk

  3. Department of Biochemistry, The University of Western Ontario, London, Ontario, Canada

    F A Dick & G S Shaw

  4. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada

    D P Bazett-Jones

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Correspondence to J S Mymryk.

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Yousef, A., Fonseca, G., Pelka, P. et al. Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation. Oncogene 29, 4693–4704 (2010). https://doi.org/10.1038/onc.2010.226

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