Cyclin-dependant kinase (CDK) orders the cell cycle via substrate specific thresholds

ABSTRACT: The appropriate ordering of the cell cycle events in eukaryoates is thought to be brought about by qualitative differences in the substrate specificity of multiple differentially expression Cyclin-CDK complexes. Our analysis of fission yeast supports an alternative quantitative model. Here we report a phosphoproteomics based global analysis of CDK substrate phosphorylation. We show that the phosphorylation of different CDK substrates is precisely ordered during the cell cycle by a single Cyclin-CDK complex. This is achieved by the differential sensitivity of substrates to a progressively rising CDK-to-phosphatase activity ratio, with early-phosphorylated substrates more sensitive to CDK activity than late substrates. This is combined with a rapid substrate phosphorylation turnover to generate clearly resolved substrate-specific thresholds, which in turn ensures the temporal ordering of downstream cell cycle events. These observations can also explain the major genetic redundancies between different cyclins and CDKs in higher eukaryotes.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Schizosaccharomyces Pombe

SUBMITTER: Andrew Jones  

LAB HEAD: Ambrosius P. Snijders

PROVIDER: PXD003598 | Pride | 2018-04-11

REPOSITORIES: Pride