A mathematical description of regulation of the G1-S transition of the mammalian cell cycle

Model Status

This CellML model has been recoded to remove the reaction element. The model opens in PCEnv and COR but unfortunately it does not run due to there being 'circular arguments' (COR) or the model being 'under-constrained' (PCEnv). At the moment this is a limitation of the simulation software because it is unable to process nonlinear algebraic equations that must be solved iteratively at each time step.

Model Structure

In order to better understand developmental and tumour biology, extensive research on the control of the mammalian cell cycle is being carried out. At the protein level, several molecules play a role in the control of the G1-S transition of the cell cycle. Specifically, G1 cyclins such as cyclin E are known to form phosphorylated complexes with cyclin dependent kinases (cdk's, such as cdk2). These complexes, which can be inhibited by other proteins, can phosphorylate pocket proteins such as pRb. Hyperphosphorylation of pRb occurs at the time of E2F-1 release. This transcription factor initiates the transcription of genes involved in S phase activities, including DNA polymerase.

Hatzimanikatis, Lee and Bailey capture the components and interactions of cyclin E, cdk2, pRb, inhibitor and E2F-1 during the G1-S transition of the cell cycle in their mathematical model (see the figure below).

The complete original paper reference is cited below:

A Mathematical Description of Regulation of the G1-S Transition of the Mammalian Cell Cycle, V. Hatzimanikatis, K. H. Lee and J. E. Bailey, 1999, Biotechnology and Bioengineering , 65, 631-637. (A PDF version of the article is available for Journal Members on the Biotechnology and Bioengineering website.) PubMed ID: 10550769

A schematic diagram of the reactions involved during the G1-S transition of the mammalian cell cycle.