Novak, Tyson, 2004

Model Status

This CellML version of the model runs in PCEnv but in order to reproduce the published results, requires initial concentrations that are not listed in the paper. The switch "mass = mass/2 when Cdh1 crosses 0.2 from below" has not been implemented in this CellML description.

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Model Structure

ABSTRACT: Inhibition of protein synthesis by cycloheximide blocks subsequent division of a mammalian cell, but only if the cell is exposed to the drug before the restriction point (i.e. within the first several hours after birth). If exposed to cycloheximide after the restriction point, a cell proceeds with DNA synthesis, mitosis and cell division and halts in the next cell cycle. If cycloheximide is later removed from the culture medium, treated cells will return to the division cycle, showing a complex pattern of division times post-treatment, as first measured by Zetterberg and colleagues.

We simulate these physiological responses of mammalian cells to transient inhibition of growth, using a set of nonlinear differential equations based on a realistic model of the molecular events underlying progression through the cell cycle. The model relieson our earlier work on the regulation of cyclin-dependent protein kinases during the cell division cycle of yeast. The yeast model is supplemented with equations describing the effects of retinoblastoma protein on cell growth and the synthesis of cyclins A and E, and with a primitive representation of the signaling pathway that controls synthesis of cyclin D.

The complete original paper reference is cited below:

A model for restriction point control of the mammalian cell cycle, Bela Novak, and John J Tyson, 2004, Journal of Theoretical Biology , 230, 563-579. (A PDF version of the article is available to subscribers on the Journal of Theoretical Biology website.) PubMed ID: 15363676

Molecular network regulating the progression of mammalian cells through the cell cycle.
Derived from workspace Novak, Tyson, 2004 at changeset cadfae101d9f.
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