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Evolutionary functional analysis and molecular regulation of the ZEB transcription factors

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Abstract

ZEB1 and ZEB2, which are members of the ZEB family of transcription factors, play a pivotal role in the development of the vertebrate embryo. However, recent evidence shows that both proteins can also drive the process of epithelial-mesenchymal transition during malignant cancer progression. The understanding of how both ZEBs act as transcription factors opens up new possibilities for future treatment of advanced carcinomas. This review gives insight into the molecular mechanisms that form the basis of the multitude of cellular processes controlled by both ZEB factors. By using an evolutionary approach, we analyzed how the specific organization of the different domains and regulatory sites in ZEB1 and ZEB2 came into existence. On the basis of this analysis, a detailed overview is provided of the different cofactors and post-translational mechanisms that are associated with ZEB protein functionality.

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Acknowledgments

This research was funded by grants from the FWO, the Geconcerteerde Onderzoeksacties of Ghent University, the Stichting tegen Kanker, Belgium, the Association for International Cancer Research (Scotland), the EU-FP6 framework program BRECOSM LSHC-CT-2004-503224, and the EU-FP7 framework program TuMIC 2008-201662. We acknowledge Dr. Amin Bredan for critical reading of the manuscript and the members of our research groups for valuable discussions.

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Authors and Affiliations

  1. Unit of Molecular and Cellular Oncology, Department for Molecular Biomedical Research, VIB, Technologiepark 927, 9052, Ghent, Belgium

    Alexander Gheldof, Bram De Craene & Geert Berx

  2. Department of Biomedical Molecular Biology, Ghent University, 9052, Ghent, Belgium

    Alexander Gheldof, Paco Hulpiau, Frans van Roy, Bram De Craene & Geert Berx

  3. Molecular Cell Biology Unit, Department for Molecular Biomedical Research, VIB, 9052, Ghent, Belgium

    Frans van Roy

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  1. Alexander Gheldof
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  2. Paco Hulpiau
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  3. Frans van Roy
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  4. Bram De Craene
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  5. Geert Berx
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Correspondence to Geert Berx.

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Gheldof, A., Hulpiau, P., van Roy, F. et al. Evolutionary functional analysis and molecular regulation of the ZEB transcription factors. Cell. Mol. Life Sci. 69, 2527–2541 (2012). https://doi.org/10.1007/s00018-012-0935-3

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  • DOI: https://doi.org/10.1007/s00018-012-0935-3

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