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Updated: Jul 26, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Mathematical analysis of binary activation of a cell cycle kinase which down-regulates its own inhibitor

C D Thron

    Biophysical Chemistry
    |July 2, 1999
    PubMed

    Insights

    The cyclin E/CDK2 (EK2) kinase and p27Kip1 (p27) protein form a feedback loop. Mathematical models suggest this loop drives a bistable system for abrupt cell cycle transitions.

    Area of Science:

    • Cell Biology
    • Biochemistry
    • Mathematical Biology

    Background:

    • Mammalian cell cycle progression from G1 to S phase is regulated by cyclin E/CDK2 (EK2).
    • p27Kip1 (p27) inhibits EK2, but EK2 can phosphorylate and deactivate p27, creating a positive-feedback loop.
    • This feedback loop is proposed to cause a binary (all-or-none) release of EK2.

    Purpose of the Study:

    • To investigate the proposed positive-feedback loop between EK2 and p27.
    • To explore the mechanism of binary release of EK2 from p27 using mathematical modeling.
    • To determine the conditions required for bistability in the EK2-p27 system.

    Main Methods:

    • Development and analysis of two mathematical models for the EK2-p27 interaction.
    • Model 1: EK2 deactivates p27 in both inhibitory complexes and free p27.
    • Model 2: EK2-catalyzed p27 deactivation exhibits saturable kinetics with respect to free p27.

    Main Results:

    • The positive-feedback loop between EK2 and p27 can lead to a bistable biochemical system.
    • Bistability is characterized by a saddle-node bifurcation, causing abrupt shifts in EK2 activity.
    • Mathematical analysis revealed conditions for bistability, including the reaction order of p27 deactivation relative to EK2 and p27.

    Conclusions:

    • The EK2-p27 feedback loop provides a mechanism for switch-like cell cycle transitions.
    • Bistability in this system relies on specific kinetic properties, particularly the reaction order of p27 deactivation.
    • Mathematical modeling is crucial for understanding the complex dynamics of cell cycle regulation.

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