Abstract
The E6 proteins from the high-risk human papillomavirus (HPV) types have previously been shown to target a number of PDZ domain-containing proteins for proteasome-mediated degradation. These include the hDlg tumour suppressor and the MAGI-1 protein. In this study we show that high-risk HPV E6 proteins also target the related MAGI-2 and MAGI-3 proteins for degradation. Moreover, we show that the interaction is specific to one PDZ domain, and that co-expression of this domain can protect each of the full-length MAGI proteins from E6-mediated degradation. These data provide clear indicators for the potential design of compounds that could specifically inhibit the interaction of oncogenic HPV E6 proteins with an important class of target proteins.
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Acknowledgements
The authors would like to thank Dr Oliviero Carugo for useful discussions. This work was supported in part by grants from the National Institutes of Health, the Department of Defense and CapCURE to C Sawyers and a grant from the Associazione Italiana per la Ricerca sul Cancro to L Banks.
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Thomas, M., Laura, R., Hepner, K. et al. Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation. Oncogene 21, 5088–5096 (2002). https://doi.org/10.1038/sj.onc.1205668
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DOI: https://doi.org/10.1038/sj.onc.1205668
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