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HPV E6 and MAGUK protein interactions: determination of the molecular basis for specific protein recognition and degradation

Oncogene volume 20, pages 5431–5439 (2001)Cite this article

Abstract

It has recently been shown that the high-risk human papillomavirus (HPV) E6 proteins can target the PDZ-domain containing proteins, Dlg, MUPP-1, MAGI-1 and hScrib for proteasome-mediated degradation. However, the E6 proteins from HPV-16 and HPV-18 (the two most common high-risk virus types) differ in their ability to target these proteins in a manner that correlates with their malignant potential. To investigate the underlying mechanisms for this, we have mutated HPV-16 and HPV-18 E6s to give each protein the other's PDZ-binding motif. Analysis of these mutants shows that the greater ability of HPV-18 E6 to bind to these proteins and to target them for degradation is indeed due to a single amino acid difference. Using a number of assays, we show that the E6 proteins interact specifically with only one of the five PDZ domains of MAGI-1, and this is the first interaction described for this particular PDZ domain. We also show that the guanylate kinase homology domain and the regions of MAGI-1 downstream of amino acid 733 are not required for the degradation of MAGI-1. Finally, in a series of comparative analyses, we show that the degradation of MAGI-1 occurs through a different mechanism from that used by the E6 protein to induce the degradation of Dlg and p53.

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Acknowledgements

This work was supported in part by a grant from the Associazione Italiana per Ricerca sul Cancro to L Banks and grant number RO1 CA58541 from the National Institutes of Health to R Yavier.

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Authors and Affiliations

  1. International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, I-34012, Italy

    Miranda Thomas, David Pim & Lawrence Banks

  2. Division of Molecular Virology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, Texas, USA

    Britt Glaunsinger & Ron Javier

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  1. Miranda Thomas
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Thomas, M., Glaunsinger, B., Pim, D. et al. HPV E6 and MAGUK protein interactions: determination of the molecular basis for specific protein recognition and degradation. Oncogene 20, 5431–5439 (2001). https://doi.org/10.1038/sj.onc.1204719

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