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Human and primate tumour viruses use PDZ binding as an evolutionarily conserved mechanism of targeting cell polarity regulators

Oncogene volume 28, pages 1–8 (2009)Cite this article

Abstract

A unique feature of the cancer-causing mucosotropic human papillomaviruses (HPVs) is the ability of their E6 proteins to interact with a number of PDZ domain-containing cellular substrates, including the cell polarity regulators hDlg and hScrib. These interactions are essential for the ability of these viruses to induce malignant progression. Rhesus papillomaviruses (RhPV) are similar to their human counterparts in that they also cause anogenital malignancy in their host, the Rhesus Macaque. However, unlike HPV E6, the RhPV E6 has no PDZ-binding motif. We now show that such a motif is present on the RhPV E7 oncoprotein. This motif specifically confers PDZ-binding activity and directs the interaction of RhPV E7 with the cell polarity regulator Par3, which it targets for proteasome-mediated degradation. These results demonstrate an amazing evolutionary conservation of function between the RhPV and the HPV oncoproteins, where both target proteins of the same cell polarity control network, although through different components and pathways.

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Acknowledgements

This work was supported in part by a research grant from the Associazione Italiana per la Ricerca sul Cancro to LB and from a Public Health Service Grant from the NIH CA103645 (MAO) to MO.

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Authors and Affiliations

  1. International Centre for Genetic Engineering and Biotechnology, Trieste, Italy

    V Tomaić, D Gardiol, P Massimi, M Myers & L Banks

  2. Department of Molecular Genetics and Microbiology, The University of New Mexico School of Medicine, Albuquerque, NM, USA

    M Ozbun

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  1. V Tomaić
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  2. D Gardiol
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  3. P Massimi
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  4. M Ozbun
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  5. M Myers
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  6. L Banks
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Correspondence to L Banks.

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

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Tomaić, V., Gardiol, D., Massimi, P. et al. Human and primate tumour viruses use PDZ binding as an evolutionarily conserved mechanism of targeting cell polarity regulators. Oncogene 28, 1–8 (2009). https://doi.org/10.1038/onc.2008.365

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