التفاصيل البيبلوغرافية
| العنوان: |
A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation. |
| المؤلفون: |
Valverde, Juan Manuel, Dubra, Geronimo, Phillips, Michael, Haider, Austin, Elena-Real, Carlos, Fournet, Aurélie, Alghoul, Emile, Chahar, Dhanvantri, Andrés-Sanchez, Nuria, Paloni, Matteo, Bernadó, Pau, van Mierlo, Guido, Vermeulen, Michiel, van den Toorn, Henk, Heck, Albert J. R., Constantinou, Angelos, Barducci, Alessandro, Ghosh, Kingshuk, Sibille, Nathalie, Knipscheer, Puck |
| المصدر: |
Nature Communications; 10/9/2023, Vol. 14 Issue 1, p1-23, 23p |
| مصطلحات موضوعية: |
PHOSPHORYLATION, MOLECULAR kinetics, CELL cycle, CONDENSATION, SYSTEMS biology, CYCLIN-dependent kinases |
| مستخلص: |
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. The authors show that dynamics of protein phosphorylation in the vertebrate cell cycle is largely attributable to CDK-mediated regulation of intrinsically disordered proteins that are involved in biomolecular condensate formation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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