4.6 Article

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

Journal

CELLS
Volume 8, Issue 12, Pages -

Publisher

MDPI
DOI: 10.3390/cells8121537

Keywords

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

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Funding

  1. National Science Centre, Poland [2017/25/B/ST1/00051, 2017/26/M/ST1/00783]
  2. Polish Ministry of National Defence Kosciuszko [571/2016/DA]

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In this paper we propose a role for the CDC6 protein in the entry of cells into mitosis. This has not been considered in the literature so far. Recent experiments suggest that CDC6, upon entry into mitosis, inhibits the appearance of active CDK1 and cyclin B complexes. This paper proposes a mathematical model which incorporates the dynamics of kinase CDK1, its regulatory protein cyclin B, the regulatory phosphatase CDC25 and the inhibitor CDC6 known to be involved in the regulation of active CDK1 and cyclin B complexes. The experimental data lead us to formulate a new hypothesis that CDC6 slows down the activation of inactive complexes of CDK1 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 CDK1 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.

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