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Dynamics of Cdk1 substrate specificity during the cell cycle.

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.

Pubmed ID: 21658602

Authors

  • Kõivomägi M
  • Valk E
  • Venta R
  • Iofik A
  • Lepiku M
  • Morgan DO
  • Loog M

Journal

Molecular cell

Publication Data

June 10, 2011

Associated Grants

  • Agency: Wellcome Trust, Id: 079014/Z/06/Z
  • Agency: NIGMS NIH HHS, Id: R01 GM069901
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Amino Acid Motifs
  • Binding Sites
  • CDC2 Protein Kinase
  • Cell Cycle
  • Consensus Sequence
  • Hydrophobic and Hydrophilic Interactions
  • Models, Biological
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Substrate Specificity