Cyclin-Specific Docking Mechanisms Reveal the Complexity of M-CDK Function in the Cell Cycle

Mol Cell. 2019 Jul 11;75(1):76-89.e3. doi: 10.1016/j.molcel.2019.04.026. Epub 2019 May 14.


Cyclin-dependent kinases (CDKs) coordinate hundreds of molecular events during the cell cycle. Multiple cyclins are involved, but the global role of cyclin-specific phosphorylation has remained unsolved. We uncovered a cyclin docking motif, LxF, that mediates binding of replication factor Cdc6 to mitotic cyclin. This interaction leads to phospho-adaptor Cks1-mediated inhibition of M-CDK to facilitate Cdc6 accumulation and sequestration in mitosis. The LxF motif and Cks1 also mediate the mutual inhibition between M-CDK and the tyrosine kinase Swe1. Additionally, the LxF motif is critical for targeting M-CDK to phosphorylate several mitotic regulators; for example, Spo12 is targeted via LxF to release the phosphatase Cdc14. The results complete the full set of G1, S, and M-CDK docking mechanisms and outline the unified role of cyclin specificity and CDK activity thresholds. Cooperation of cyclin and Cks1 docking creates a variety of CDK thresholds and switching orders, including combinations of last in, first out (LIFO) and first in, first out (FIFO) ordering.

Keywords: CDK; CDK inhibition; Saccharomyces cerevisiae; cell cycle; cyclin-dependent kinase; kinase docking; kinase specificity; mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acid Motifs
  • Binding Sites
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cyclins / genetics*
  • Cyclins / metabolism
  • G1 Phase Cell Cycle Checkpoints / genetics*
  • Gene Expression Regulation, Fungal*
  • M Phase Cell Cycle Checkpoints / genetics*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • S Phase Cell Cycle Checkpoints / genetics*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • CDC14 protein, S cerevisiae
  • CDC6 protein, S cerevisiae
  • CKS1 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cyclins
  • Nuclear Proteins
  • SPO12 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • SWE1 protein, S cerevisiae
  • Protein-Tyrosine Kinases
  • Protein Tyrosine Phosphatases