Goldbeter (1991), Minimal mitotic oscillator
April 2008, model of the month by Anika Oellrich
Original models: BIOMD0000000003 and BIOMD0000000004
| BioModels database contains several models dealing with the cell cycle and related mitotic oscillation. Besides BIOMD0000000005 [1] (see also here) or BIOMD0000000107 [2] (see also here), which are representing M-Phase in fission yeast, one of these models is BIOMD0000000003 [3] which focuses on mitosis in early amphibian embryos. As shown in figure 1, this simple model of the mitotic oscillator contains only three variables:
Cdc2 kinase is activated by cyclin when it accumulates up to a certain threshold. Both cyclin and cdc2 kinase are forming a complex which is named the M-phase-promoting factor (MPF). The degradation of cyclin, the associated inactivation of cdc2 and, subsequently, mitosis are caused by MPF. The latter leads to a new cell cycle. In addition to the three variables and to the activation and inactivation rates of cdc2 kinase and cyclin protease, respectively, there are two more rate parameters:
The behaviour of the system can be described with the following three differential equations:
| Figure 1: Bicyclic cascade model for oscillating behaviour in Mitosis. |
Figure 2: Resulting graph of the minimal mitotic oscillator (parameter values see [1]). | Figure 2 shows the resulting output graph of the minimal mitotic oscillator. The graph shows two time delays:
Cyclin (C) accumulates up to a certain value before the activation of cdc2 (M) starts, which constitutes the first time delay. The second time delay results from the fact that M also has to increase up to a threshold before it activates the cyclin protease (X). |
Bibliographic References
- J.J. Tyson. Modeling the cell division cycle: cdc2 and cyclin interactions. Proc Natl Acad Sci U S A 88:7328-7332, 1991. [SRS@EBI]
- B. Novak, J.J. Tyson. Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos. J. Cell. Sci. 106:1153-1168, 1993. [SRS@EBI]
- A. Goldbeter. A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase. Proc Natl Acad Sci U S A 88:9107-9111, 1991. [SRS@EBI]