Phosphorylation as a phase separation switch during the cell cycle

The cell cycle is driven by cyclin-dependent kinases (CDKs). How the global changes in protein phosphorylation mediated by CDKs promote a rapid and ordered cell reorganisation at mitosis onset has long been a mystery. Here, Valverde, Dubra and a consortium led by the Fisher lab (IGMM) and Altelaar lab (University of Utrecht) 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. In other words, CDKs promote assembly of, or dissolve, membraneless organelles by phosphorylating key proteins and controlling their phase separation.

The article was published in Nature communications on the 9th October 2023.

Valverde, J.-M.†, Dubra, G.†, van den Toorn, H., van Mierlo, G., Vermeulen, M., Heck, A.J.R., Elena-Real, C., Fournet, A., Al Ghoul, E., Chahar, D., Haider, A., Paloni, M., Constantinou, A., Barducci, A., Ghosh, K., Sibille, N., Bernado, P., Knipscheer, P., Krasinska, L.‡, Fisher, D.‡*, Altelaar, M.‡* (2023) A Cyclin dependent kinase-mediated phosphorylation switch of disordered protein condensation. Nat Commun 14, 6316. https://doi.org/10.1038/s41467-023-42049-0. †‡ Equal contributions. *Corresponding authors.