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Title: A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation
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 singleXenopusembryos, 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.  more » « less
Award ID(s):
2213103
PAR ID:
10525764
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more » ; ; ; « less
Publisher / Repository:
Nature Publishing Group
Date Published:
Journal Name:
Nature Communications
Volume:
14
Issue:
1
ISSN:
2041-1723
Subject(s) / Keyword(s):
phase separation biomolecular condensates cell cycle mitosis meiosis phosphorylation kinase cyclin intrinsically disordered protein
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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