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A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation

Author

Listed:
  • Juan Manuel Valverde

    (University of Utrecht, Utrecht
    Netherlands Proteomics Center)

  • Geronimo Dubra

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Michael Phillips

    (University of Denver)

  • Austin Haider

    (University of Denver)

  • Carlos Elena-Real

    (CBS, CNRS, University of Montpellier, INSERM)

  • Aurélie Fournet

    (CBS, CNRS, University of Montpellier, INSERM)

  • Emile Alghoul

    (IGH, CNRS, University of Montpellier)

  • Dhanvantri Chahar

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Nuria Andrés-Sanchez

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Matteo Paloni

    (University of Denver)

  • Pau Bernadó

    (CBS, CNRS, University of Montpellier, INSERM)

  • Guido Mierlo

    (Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen)

  • Michiel Vermeulen

    (Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen)

  • Henk Toorn

    (University of Utrecht, Utrecht
    Netherlands Proteomics Center)

  • Albert J. R. Heck

    (University of Utrecht, Utrecht
    Netherlands Proteomics Center)

  • Angelos Constantinou

    (IGH, CNRS, University of Montpellier)

  • Alessandro Barducci

    (CBS, CNRS, University of Montpellier, INSERM)

  • Kingshuk Ghosh

    (University of Denver
    University of Denver)

  • Nathalie Sibille

    (CBS, CNRS, University of Montpellier, INSERM)

  • Puck Knipscheer

    (Oncode Institute, Hubrecht Institute–KNAW and University Medical Center)

  • Liliana Krasinska

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Daniel Fisher

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Maarten Altelaar

    (University of Utrecht, Utrecht
    Netherlands Proteomics Center)

Abstract

Cell cycle transitions result from global changes in protein phosphorylation states triggered by cyclin-dependent kinases (CDKs). To understand how this complexity produces an ordered and rapid cellular reorganisation, we generated a high-resolution map of changing phosphosites throughout unperturbed early cell cycles in single Xenopus embryos, derived the emergent principles through systems biology analysis, and tested them by biophysical modelling and biochemical experiments. We found that most dynamic phosphosites share two key characteristics: they occur on highly disordered proteins that localise to membraneless organelles, and are CDK targets. Furthermore, CDK-mediated multisite phosphorylation can switch homotypic interactions of such proteins between favourable and inhibitory modes for biomolecular condensate formation. These results provide insight into the molecular mechanisms and kinetics of mitotic cellular reorganisation.

Suggested Citation

  • Juan Manuel Valverde & Geronimo Dubra & Michael Phillips & Austin Haider & Carlos Elena-Real & Aurélie Fournet & Emile Alghoul & Dhanvantri Chahar & Nuria Andrés-Sanchez & Matteo Paloni & Pau Bernadó , 2023. "A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42049-0
    DOI: 10.1038/s41467-023-42049-0
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    References listed on IDEAS

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