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The hScrib/Dlg apico-basal control complex is differentially targeted by HPV-16 and HPV-18 E6 proteins

Oncogene volume 24, pages 6222–6230 (2005)Cite this article

Abstract

The E6 proteins of the high-risk Human papillomaviruses (HPV) types have a well-documented ability to target certain cellular proteins for ubiquitin-mediated degradation via the proteasome. Previous studies have shown that E6 proteins interact differently with different target proteins, and that the viral proteins, depending upon the target, may recruit diverse cellular ubiquitin-protein ligases. In this study, we have examined the abilities of E6 proteins from HPV-16 and HPV-18 to interact with and induce the degradation of two PDZ domain-containing targets, Dlg and hScrib. We have also mapped the binding site of E6 on hScrib and shown that the interaction of E6 with hScrib is distinct from its interactions with other PDZ domain-containing targets. This is reflected in the efficiency with which the two viral E6 proteins can inhibit hScrib's suppression of cell transformation.Dlg and hScrib have complementary activities in the control of epithelial cell polarity and the fact that both are targeted by high-risk HPV E6 proteins underlines their importance. Our finding that they are each targeted differently by HPV-16 and HPV-18 E6s suggests that the two viruses are subjected to somewhat different constraints and provides a possible explanation for the apparent redundancy in targeting both parts of this important control mechanism.

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Acknowledgements

We are grateful to Marleen Petit for the kind gift of the 4PDZ constructs and we thank David Pim and Helena Sterlinko for comments on the manuscript. This work was supported in part by a grant from the Associazione Italiana per La Ricerca sul Cancro to LB and J-PB is funded by INSERM, Institut Paoli-Calmettes, La Ligue Contre Le Cancer (Label Ligue) and ACI ‘Jeune Chercheur’. CN is the recipient of a fellowship from Conseil Général.

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

    Miranda Thomas, Paola Massimi & Lawrence Banks

  2. Molecular Pharmacology, Institut de Recherches sur le Cancer de Marseille, UMR 599 Inserm-Institut Paoli-Calmettes, 27 boulevard Leï Roure, Marseille, 13009, France

    Christel Navarro & Jean-Paul Borg

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  1. Miranda Thomas
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Correspondence to Lawrence Banks.

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Thomas, M., Massimi, P., Navarro, C. et al. The hScrib/Dlg apico-basal control complex is differentially targeted by HPV-16 and HPV-18 E6 proteins. Oncogene 24, 6222–6230 (2005). https://doi.org/10.1038/sj.onc.1208757

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