CDK Substrate Phosphorylation and Ordering the Cell Cycle
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 phosp...
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Veröffentlicht in: | Cell 2016-12, Vol.167 (7), p.1750-1761.e16 |
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Sprache: | eng |
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Zusammenfassung: | 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.
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•Global analysis of CDK substrates and their phosphorylation dynamics in fission yeast•CDK substrate phosphorylation can be temporally ordered by a single cyclin-CDK•Substrate-specific activity thresholds set phosphorylation timing and cell-cycle order•Cyclin-substrate specificity provides a secondary, more minor, level of regulation
A systems analysis of CDK substrates in yeast shows that the phosphorylation of different CDK substrates can be temporally ordered during the cell cycle by a single cyclin-CDK via rising CDK activity and the differential sensitivity of substrates to CDK activity. |
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ISSN: | 0092-8674 1097-4172 1097-4172 |
DOI: | 10.1016/j.cell.2016.11.034 |