S phase and mitotic onset are brought about by the action of multiple different cyclin-CDK complexes. However, it has been suggested that changes in the total level of CDK kinase activity, rather than substrate specificity, drive the temporal ordering of S phase and mitosis. Here, we present a phosphoproteomics-based systems analysis of CDK substrates in fission yeast and demonstrate that the phosphorylation of different CDK substrates can be temporally ordered during the cell cycle by a single cyclin-CDK. This is achieved by rising CDK activity and the differential sensitivity of substrates to CDK activity over a wide dynamic range. This is combined with rapid phosphorylation turnover to generate clearly resolved substrate-specific activity thresholds, which in turn ensures the appropriate ordering of downstream cell-cycle events. Comparative analysis with wild-type cells expressing multiple cyclin-CDK complexes reveals how cyclin-substrate specificity works alongside activity thresholds to fine-tune the patterns of substrate phosphorylation.
Pubmed ID: 27984725 RIS Download
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View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets Mouse IgG
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View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets V5-TAG
View all literature mentionsThis unknown targets cdc2, phospho (Tyr15)
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets V5-TAG
View all literature mentionsThis unknown targets cdc2, phospho (Tyr15)
View all literature mentions