title: A model for restriction point control of the mammalian cell cycle.
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 relies on 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.
authors.affiliation: Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Gellert ter 4, 1521 Budapest, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Novák
authors.forename: John J
authors.initials: JJ
authors.lastname: Tyson
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D008322:Mammals / Q000502:physiology*; D008954:Models, Biological; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000494:pharmacology
chemical_list: D011500:Protein Synthesis Inhibitors; D016160:Retinoblastoma Protein; D003513:Cycloheximide; D018844:Cyclin-Dependent Kinases