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Mol Cell. 2011 Jun 10;42(5):610-23. doi: 10.1016/j.molcel.2011.05.016.

Dynamics of Cdk1 substrate specificity during the cell cycle.

Author information

1
Institute of Technology, University of Tartu, Tartu 50411, Estonia. mart.loog@ut.ee

Abstract

Cdk specificity is determined by the intrinsic selectivity of the active site and by substrate docking sites on the cyclin subunit. There is a long-standing debate about the relative importance of these factors in the timing of Cdk1 substrate phosphorylation. We analyzed major budding yeast cyclins (the G1/S-cyclin Cln2, S-cyclin Clb5, G2/M-cyclin Clb3, and M-cyclin Clb2) and found that the activity of Cdk1 toward the consensus motif increased gradually in the sequence Cln2-Clb5-Clb3-Clb2, in parallel with cell cycle progression. Further, we identified a docking element that compensates for the weak intrinsic specificity of Cln2 toward G1-specific targets. In addition, Cln2-Cdk1 showed distinct consensus site specificity, suggesting that cyclins do not merely activate Cdk1 but also modulate its active-site specificity. Finally, we identified several Cln2-, Clb3-, and Clb2-specific Cdk1 targets. We propose that robust timing and ordering of cell cycle events depend on gradual changes in the substrate specificity of Cdk1.

PMID:
21658602
PMCID:
PMC3115021
DOI:
10.1016/j.molcel.2011.05.016
[Indexed for MEDLINE]
Free PMC Article
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