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Functionally distinct monomers and trimers produced by a viral oncoprotein

Oncogene volume 27, pages 1412–1420 (2008)Cite this article

Abstract

While the process of homo-oligomer formation and disassembly into subunits represents a common strategy to regulate protein activity, reports of proteins in which the subunit and homo-oligomer perform independent functions are scarce. Tumorigenesis induced by the adenovirus E4-ORF1 oncoprotein depends on its binding to a select group of cellular PDZ proteins, including MUPP1, MAGI-1, ZO-2 and Dlg1. We report here that in cells E4-ORF1 exists as both a monomer and trimer and that monomers specifically bind and sequester MUPP1, MAGI-1 and ZO-2 within insoluble complexes whereas trimers specifically bind Dlg1 and promote its translocation to the plasma membrane. This work exposes a novel strategy wherein the oligomerization state of a protein not only determines the capacity to bind separate related targets but also couples the interactions to different functional consequences.

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Acknowledgements

We thank Andy Rice and Chris Herrmann for use of their FPLC system and Richard Sutton for retroviral vector plasmids. RSW and KKF were supported by predoctoral fellowships from the US. Army (Breast Cancer Training Grant DAMD17-94 J4204) and the National Cancer Institute (Viral Oncology Training Grant T32 CA09197). This research was funded by Public Health Service Grants CA58541 (RTJ) and AI36040 (BVVP).

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Author notes

  1. S-H Chung

    Present address: 3Current address: McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.,

  2. R S Weiss

    Present address: 4Current address: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.,

  3. K K Frese

    Present address: 5Current address: Cancer Research UK, Cambridge Research Institute, Cambridge CB2 0RE, UK.,

Authors and Affiliations

  1. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

    S-H Chung, R S Weiss, K K Frese & R T Javier

  2. Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA

    B V V Prasad

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  1. S-H Chung
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  2. R S Weiss
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  3. K K Frese
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  4. B V V Prasad
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  5. R T Javier
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Corresponding author

Correspondence to R T Javier.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Chung, SH., Weiss, R., Frese, K. et al. Functionally distinct monomers and trimers produced by a viral oncoprotein. Oncogene 27, 1412–1420 (2008). https://doi.org/10.1038/sj.onc.1210784

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