RT Journal Article
SR Electronic
T1 Cyclin A and Cks1 promote kinase consensus switching to non-proline directed CDK1 phosphorylation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.24.493195
DO 10.1101/2022.05.24.493195
A1 Aymen al-Rawi
A1 Svitlana Korolchuk
A1 Jane Endicott
A1 Tony Ly
YR 2022
UL http://biorxiv.org/content/early/2022/05/24/2022.05.24.493195.abstract
AB 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 alters substrate choice, with intermediate and low sensitivity CDK1 substrates enriched in DNA replication and mitotic functions, respectively. This activity dependence was 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 promote 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.Competing Interest StatementThe authors have declared no competing interest.