Reference - PMID:27984725 - CDK Substrate Phosphorylation and Ordering the Cell Cycle.
Reference summary
- PubMed ID
- PMID:27984725
- Title
- CDK Substrate Phosphorylation and Ordering the Cell Cycle.
- Authors
- Swaffer MP, Jones AW, Flynn HR, Snijders AP, Nurse P
- Citation
- Cell 2016 Dec 15;167(7):1750-1761.e16
- Publication year
- 2016
- Abstract
- 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.
