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

Cyclin-Dependent Kinases / metabolism Phosphorylation Cell Cycle Proteins / metabolism Cell Cycle Cyclin-Dependent Kinase 2 / metabolism

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
09 10 2023

Historique:

received: 05 07 2023

accepted: 28 09 2023

medline: 2 11 2023

pubmed: 10 10 2023

entrez: 9 10 2023

Statut: epublish

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.

Identifiants

DOI: 10.1038/s41467-023-42049-0 PMID: 37813838 PMC: PMC10562473

pubmed: 37813838

doi: 10.1038/s41467-023-42049-0

pii: 10.1038/s41467-023-42049-0

pmc: PMC10562473

doi:

Substances chimiques

Cyclin-Dependent Kinases EC 2.7.11.22

Cell Cycle Proteins 0

Cyclin-Dependent Kinase 2 EC 2.7.11.22

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

6316

Subventions

Organisme : NIGMS NIH HHS

ID : R01 GM138901

Pays : United States

Informations de copyright

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