Quantitative model of eukaryotic Cdk control through the Forkhead CONTROLLER

NPJ Syst Biol Appl. 2021 Jun 11;7(1):28. doi: 10.1038/s41540-021-00187-5.

Abstract

In budding yeast, synchronization of waves of mitotic cyclins that activate the Cdk1 kinase occur through Forkhead transcription factors. These molecules act as controllers of their sequential order and may account for the separation in time of incompatible processes. Here, a Forkhead-mediated design principle underlying the quantitative model of Cdk control is proposed for budding yeast. This design rationalizes timing of cell division, through progressive and coordinated cyclin/Cdk-mediated phosphorylation of Forkhead, and autonomous cyclin/Cdk oscillations. A "clock unit" incorporating this design that regulates timing of cell division is proposed for both yeast and mammals, and has a DRIVER operating the incompatible processes that is instructed by multiple CLOCKS. TIMERS determine whether the clocks are active, whereas CONTROLLERS determine how quickly the clocks shall function depending on external MODULATORS. This "clock unit" may coordinate temporal waves of cyclin/Cdk concentration/activity in the eukaryotic cell cycle making the driver operate the incompatible processes, at separate times.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle
  • Cyclin-Dependent Kinases* / genetics
  • Cyclin-Dependent Kinases* / metabolism
  • Eukaryotic Cells* / metabolism
  • Phosphorylation
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism

Substances

  • Cyclin-Dependent Kinases