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Lookup NU author(s): Svitlana Korolchuk, Professor Jane Endicott
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 The Author(s)Ordered protein phosphorylation by CDKs is a key mechanism for regulating the cell cycle. How temporal order is enforced in mammalian cells remains unclear. Using a fixed cell kinase assay and phosphoproteomics, we show how CDK1 activity and non-catalytic CDK1 subunits contribute to the choice of substrate and site of phosphorylation. Increases in CDK1 activity alter substrate choice, with intermediate- and low-sensitivity CDK1 substrates enriched in DNA replication and mitotic functions, respectively. This activity dependence is shared between Cyclin A- and Cyclin B-CDK1. Cks1 has a proteome-wide role as an enhancer of multisite CDK1 phosphorylation. Contrary to the model of CDK1 as an exclusively proline-directed kinase, we show that Cyclin A and Cks1 enhance non-proline-directed phosphorylation, preferably on sites with a +3 lysine residue. Indeed, 70% of cell-cycle-regulated phosphorylations, where the kinase carrying out this modification has not been identified, are non-proline-directed CDK1 sites.
Author(s): al-Rawi A, Kaye E, Korolchuk S, Endicott JA, Ly T
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2023
Volume: 42
Issue: 3
Print publication date: 28/03/2023
Online publication date: 24/02/2023
Acceptance date: 02/02/2023
Date deposited: 09/03/2023
ISSN (electronic): 2211-1247
Publisher: Cell Press
URL: https://doi.org/10.1016/j.celrep.2023.112139
DOI: 10.1016/j.celrep.2023.112139
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