A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation
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Published:2023-10-09
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Valverde Juan ManuelORCID, Dubra GeronimoORCID, Phillips MichaelORCID, Haider Austin, Elena-Real Carlos, Fournet Aurélie, Alghoul EmileORCID, Chahar Dhanvantri, Andrés-Sanchez Nuria, Paloni MatteoORCID, Bernadó PauORCID, van Mierlo GuidoORCID, Vermeulen MichielORCID, van den Toorn HenkORCID, Heck Albert J. R.ORCID, Constantinou AngelosORCID, Barducci AlessandroORCID, Ghosh Kingshuk, Sibille NathalieORCID, Knipscheer PuckORCID, Krasinska LilianaORCID, Fisher DanielORCID, Altelaar MaartenORCID
Abstract
AbstractCell 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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