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Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein: enhancement of transformation and transactivation

Oncogene volume 18, pages 5620–5630 (1999)Cite this article

Abstract

The high risk human papillomavirus (HPV) type 16 E7 protein affects cell growth control and promotes transformation by interfering with functions of cellular proteins. A key target of E7 is the tumor suppressor protein p105RB. Although this interaction is required for E7-dependent transformation, other cellular molecules must also be involved, because some E7 mutants that have reduced transforming abilities still bind to p105RB. In order to identify additional proteins that interact with E7 and that may be responsible to mediate its transforming function, we have used the C-terminal half of E7 in a yeast two-hybrid screen. We identified the fork head domain transcription factor M phase phosphoprotein 2 (MPP2) as an interaction partner of E7. Specific interaction of the two proteins both in vitro and in vivo in mammalian cells was detected. The interaction of MPP2 with E7 is functionally relevant since MPP2 enhances the E7/Ha-Ras co-transformation of rat embryo fibroblasts. In addition HPV16 E7, but neither non-transforming mutants of HPV16 E7 nor low risk HPV6 E7, was able to stimulate MPP2-specific transcriptional activity. Thus, MPP2 is a potentially important target for E7-mediated transformation.

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Acknowledgements

We thank S Andrecht, C Cerni, P Chambon, C Dang, L Hengst, T Kouzarides, J Mägert, WC Phelps, S Reed and I Wierstra for reagents, plasmids, cDNA libraries and sequencing and D Litchfield, J Ferrell and I Wierstra for critically reading the manuscript. F Pirollet acknowledges continuous support by D Job. This work was supported by fellowships from the Association pour la Recherche sur la Cancer and the Fondation pour la Recherche Médicale (to JM Westendorf), by a fellowship from the Boehringer Ingelheim Fonds (to J Zwicker), by the Institut National de la Santé et de la Recherche Médicale (to F Pirollet), the Dr Mildred Scheel Stiftung (to B Lüscher and R Müller), the Fonds der Chemischen Industrie (to B Lüscher), and by grants from the Deutsche Forschungsgemeinschaft (to JM Lüscher-Firzlaff and R Müller).

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Author notes

  1. Joanne M Westendorf

    Present address: Department of Molecular Pharmacology, Stanford Medical Center, 300 Pasteur Drive, Palo Alto, California, CA 94304-5332, USA

  2. Jörk Zwicker

    Present address: HHMI, Molecular and Cellular Biology, University of California at Berkeley, Berkeley, California, CA 94720, USA

  3. Marie Henriksson

    Present address: Microbiology and Tumorbiology Center, Karolinska Institute, 17177, Stockholm, Sweden

Authors and Affiliations

  1. Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany

    Juliane M Lüscher-Firzlaff, Hannelore Burkhardt, Marie Henriksson & Bernhard Lüscher

  2. INSERM U366, DBMS/Laboratoire du Cytosquelette, CEA/Grenoble, 17 rue des Martyrs, Grenoble, Cedex 9, 38054, France

    Joanne M Westendorf & Fabienne Pirollet

  3. Institut für Molekularbiologie und Tumorforschung, Universität Marburg, Emil-Mannkopff-Strasse 2, Marburg, 35037, Germany

    Jörk Zwicker & Rolf Müller

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Lüscher-Firzlaff, J., Westendorf, J., Zwicker, J. et al. Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein: enhancement of transformation and transactivation. Oncogene 18, 5620–5630 (1999). https://doi.org/10.1038/sj.onc.1202967

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