Cited by 33Microtubule and mitosis dynamicsRNA Research and SplicingGenomics and Chromatin Dynamics

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

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Valverde, Juan Manuel, Dubra, Geronimo, Phillips, Michael, Haider, Austin, Elena-Real, Carlos, Fournet, Aurélie, Alghoul, Emile, Chahar, Dhanvantri +15 more·2023·Nature Communications

Published version of a preprint

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.

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Authors
Valverde, J. M., Dubra, G., Phillips, M., Haider, A., Elena-Real, C., Fournet, A., Alghoul, E., Chahar, D., Andrés-Sanchez, N., Paloni, M., Bernadó, P., van Mierlo, G., Vermeulen, M., van den Toorn, H., Heck, A. J. R., Constantinou, A., Barducci, A., Ghosh, K., Sibille, N., Knipscheer, P., Krasinska, L., Fisher, D., & Altelaar, M.
Affiliations
  • Utrecht University (NL)
  • Centre National de la Recherche Scientifique (FR)
  • University of Denver (US)
  • Radboud University Nijmegen (NL)
  • University Medical Center Utrecht (NL)
Corresponding author
  • Fisher, Daniel
  • Altelaar, Maarten
Venue
Nature Communications
Published
2023-10-09
Volume
14
Issue
1
Pages
6316-6316
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4387448749
Cited by
33
References
145
Citations by year
2026: 7 · 2025: 11 · 2024: 9 · 2023: 4 · 2022: 2
FWCI
4.49
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
  • HAL (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • National Science Foundation (2213103)
  • Technische Universität Kaiserslautern
  • Agence Nationale de la Recherche (France2030, ANR-10-INBS-04-01, ANR-10- INBS-05, 10-INBS-04-01, ANR‐10_INBS‐04, ANR-17, ANR-10, ANR-17-CE11-0022)
  • Institut National de la Santé et de la Recherche Médicale
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (184.034.019)
  • Fondation ARC pour la Recherche sur le Cancer
  • KWF Kankerbestrijding
  • Universidad de Costa Rica (ANR-10-INBS-04)
  • Institut National Du Cancer (PLBIO18-094, PLBIO18)
  • Ministerio de Ciencia Tecnología y Telecomunicaciones
  • Université de Montpellier
  • French Infrastructure for Integrated Structural Biology (ANR-10-INBS-0.5)
  • Oncode Institute
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM138901)
  • Division of Materials Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
cyclin-dependent kinases, protein phosphorylation, intrinsically disordered proteins, biomolecular condensates, multisite phosphorylation, homotypic interactions, cell cycle, phosphosites, Xenopus embryo, biophysical model
MeSH terms
Cell Cycle, Phosphorylation, Cell Cycle Proteins, Cyclin-Dependent Kinases, Cyclin-Dependent Kinase 2

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