Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms
Figure 14
Growth-factor-induced switch in the pattern of entrainment of the cell cycle by the circadian clock.
The curves show the time evolution of cyclin A/Cdk2 (green) and cyclin B/Cdk1 (red), as well as the LD cycle (dashed line). The Cdk network is coupled to the circadian clock through Wee1 and cyclin E, for μ = 0.028 —for this value of the coupling strength the domains of entrainment to 24 h or 48 h are very close to each other in the diagram of Fig. 9D. In these conditions a decrease in the level of the growth factor GF in t = 240 h (arrow) from 1 µM to 0.3 µM lengthens the autonomous period of the cell cycle from 21.6 h to 23.0 h. The rise in period associated with the decrease in GF results in shifting the period of the entrained cell cycle from 24 h to 48 h. Parameter values are as in Fig. 9D. The scaling parameter eps is equal to 15 (see Methods).