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Cell. 2016 Dec 15;167(7):1750-1761.e16. doi: 10.1016/j.cell.2016.11.034.

CDK Substrate Phosphorylation and Ordering the Cell Cycle.

Author information

1
Cell Cycle Laboratory, The Francis Crick Institute, London NW1 1AT, UK. Electronic address: matthew.swaffer@crick.ac.uk.
2
Cell Cycle Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Protein Analysis and Proteomics Platform, The Francis Crick Institute, London NW1 1AT, UK.
3
Protein Analysis and Proteomics Platform, The Francis Crick Institute, London NW1 1AT, UK.
4
Cell Cycle Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Laboratory of Yeast Genetics and Cell Biology, Rockefeller University, New York, NY 10065, USA.

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.

KEYWORDS:

CDK; S phase; cell cycle; cyclin-dependent kinase; kinase; mitosis; phosphoproteomics; phosphorylation

PMID:
27984725
PMCID:
PMC5161751
DOI:
10.1016/j.cell.2016.11.034
[Indexed for MEDLINE]
Free PMC Article

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