Modeling the Cell Division Cycle:cdc2 and Cyclin Interactions

Model Status

This CellML version of the model has been checked in COR and PCEnv and the model runs to replicate the results in the original published paper. The units have been checked and are consistent. A PCEnv session file which reproduces Fig3a from the publication is also available for this model.

Model Structure

The cell cycle is an ordered set of events which results in cell growth and division into two identical daughter cells (somatic cell division). This sequence of specific events includes cell growth, protein, DNA, and organelle replication, and nuclear (chromosomes separate during mitosis) and cellular (the cytoplasm divides during cytokinesis) division. The control of cell division, and thus tissue growth, is complex. Maturation promoting factor (MPF) plays an important role in the control of the cell cycle. This enzyme is a heterodimer composed of cyclin and a protein kinase called cdc2. The interplay between cyclin and cdc2 in generating MPF activity is understood in some detail (see the figure below). Cyclin and cdc2 bind to form an inactive MPF complex. This complex is then activated by auto-dephosphorylation of the cdc2 subunit. Active MPF stimulates several processes which are known to be essential for nuclear and cell division. MPF then dissociates and cyclin is degraded. The cycle then repeats itself.

In a study published by John Tyson in 1991, a mathematical model of the cell cycle is developed. The author acknowledges that the model is a simplification of the real biological situation, but he explains that it is a sufficient first approximation to the cell cycle regulatory network. Agreement between experimental data and simulation results provide support for the overall scheme of the model, even if specific details are questioned. However, as understanding of the mechanisms underlying cell cycle regulation improves, mathematical models will play an increasingly important role in integrating molecular level events with cell level division.

The complete original paper reference is cited below:

Modeling the cell division cycle: cdc2 and cyclin interactions, John J. Tyson, 1991, Proceedings of the National Academy of Sciences , 88, 7328-7332. (A PDF version of the article is available to subscribers on the journal website.) PubMed ID: 1831270

A schematic diagram of the interactions between cyclin and cdc2 during the cell cycle.