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25 novembre 2020: 1 événement

  • Département Biochimie, Biophysique et Biologie Structurale

    Mercredi 25 novembre 11:00-12:00 - Tobias Madl - Univ. Graz, Autriche

    Regulation of FOX transcription factors by b-catenin

    Résumé :

    Transcription factors harbour defined intrinsically disordered regulatory regions, which raises the question of how they mediate binding to structured co-regulators and how this regulates activity. Here, we present a detailed molecular regulatory mechanism of Forkhead box transcription factors by the structured transcriptional co-regulator β-catenin. We find that the largely disordered regions of FOXP2 and FOXO4 bind β-catenin through multiple defined interaction sites, and this is regulated by post-translational modifications. In Case of FOXO4, binding of β-catenin competes with the auto-inhibitory interaction of the FOXO4 disordered region with its DNA-binding forkhead domain, and thereby enhances FOXO4 transcriptional activity. Furthermore, we show how regulators can switch between different transcription complexes, for example between anti-proliferative FOXO and pro-proliferative Wnt/TCF/LEF signalling. Together these data illustrate how the interplay of intrinsically disordered regions, post-translational modifications and co-factor binding contribute to transcription factor function.

    Selected publications on that topic :
    - Nonclassical nuclear localization signals mediate nuclear import of CIRBP.
    Bourgeois B, et al. Proc Natl Acad Sci U S A. 2020.
    doi : 10.1073/pnas.1918944117
    - Probing Surfaces in Dynamic Protein Interactions.
    Spreitzer E, et al. J Mol Biol. 2020.
    doi : 10.1016/j.jmb.2020.02.032
    - Regulation of cellular senescence via the FOXO4-p53 axis.
    Bourgeois B, Madl T. FEBS Lett. 2018.
    doi : 10.1002/1873-3468.13057
    - Phase Separation of FUS Is Suppressed by Its Nuclear Import Receptor and Arginine Methylation.
    Hofweber M, et al. Cell. 2018.
    doi : 10.1016/j.cell.2018.03.004

    CV :

    Lieu : Visio-BBB -

    En savoir plus : Département Biochimie, Biophysique et Biologie Structurale