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Article Dans Une Revue Nature Communications Année : 2023

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

Juan Manuel Valverde
Geronimo Dubra
Michael Phillips
Austin Haider
  • Fonction : Auteur
Carlos Elena-Real
  • Fonction : Auteur
Aurélie Fournet
  • Fonction : Auteur
Emile Alghoul
Dhanvantri Chahar
  • Fonction : Auteur
Nuria Andrés-Sanchez
  • Fonction : Auteur
Matteo Paloni
Pau Bernadó
Guido van Mierlo
Michiel Vermeulen
Henk van den Toorn
Albert Heck
Angelos Constantinou
Alessandro Barducci
Kingshuk Ghosh
  • Fonction : Auteur
Puck Knipscheer
Liliana Krasinska
Daniel Fisher
Maarten Altelaar

Résumé

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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Dates et versions

hal-04239889 , version 1 (12-10-2023)

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Citer

Juan Manuel Valverde, Geronimo Dubra, Michael Phillips, Austin Haider, Carlos Elena-Real, et al.. A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation. Nature Communications, 2023, 14 (1), pp.6316. ⟨10.1038/s41467-023-42049-0⟩. ⟨hal-04239889⟩
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