Mathematical Model Explaining the Role of CDC6 in the Diauxic Growth of CDK1 Activity during the M-Phase of the Cell Cycle

Cells. 2019 Nov 28;8(12):1537. doi: 10.3390/cells8121537.

Abstract

In this paper we propose a role for the CDC 6 protein in the entry of cells into mitosis. This has not been considered in the literature so far. Recent experiments suggest that CDC 6 , upon entry into mitosis, inhibits the appearance of active CDK 1 and cyclin B complexes. This paper proposes a mathematical model which incorporates the dynamics of kinase CDK 1 , its regulatory protein cyclin B, the regulatory phosphatase CDC 25 and the inhibitor CDC 6 known to be involved in the regulation of active CDK 1 and cyclin B complexes. The experimental data lead us to formulate a new hypothesis that CDC 6 slows down the activation of inactive complexes of CDK 1 and cyclin B upon mitotic entry. Our mathematical model, based on mass action kinetics, provides a possible explanation for the experimental data. We claim that the dynamics of active complexes CDK 1 and cyclin B have a similar nature to diauxic dynamics introduced by Monod in 1949. In mathematical terms we state it as the existence of more than one inflection point of the curve defining the dynamics of the complexes.

Keywords: CDC 6; CDK 1; M-phase entry; Xenopus laevis embryo; cell cycle; diauxic dynamics; dynamical system; mathematical model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Biomarkers
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division* / genetics
  • Mitosis*
  • Models, Biological
  • Models, Theoretical*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Xenopus
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*

Substances

  • Biomarkers
  • Cell Cycle Proteins
  • Xenopus Proteins
  • Protein Kinases
  • CDK1 protein, Xenopus