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

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, Guido van Mierlo, Michiel Vermeulen, Henk van den Toorn, Albert J.R. Heck, Angelos Constantinou, Alessandro Barducci, Kingshuk Ghosh, Nathalie Sibille, Puck KnipscheerLiliana Krasinska, Daniel Fisher*, Maarten Altelaar*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number6316
Pages (from-to)1-23
Number of pages23
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 9 Oct 2023

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