Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms
Figure 9
Entrainment of the cell cycle at 24 h or 48 h by the circadian clock through multiple modes of coupling.
(A) Domains of entrainment through the kinase Wee1 in the presence of a basal rate of synthesis of the protein, vswee1 = 0.06 µM h−1. (B) Entrainment through the Cdk inhibitor p21. (C) Entrainment through the circadian regulation of the synthesis of cyclin E. (D) Entrainment of the cell cycle by the circadian clock through Wee1 and cyclin E. (E) Entrainment through Wee1 and p21. (F) Entrainment through Wee1, p21, and cyclin E. The black dot in (F) refers to the conditions in which entrainment through multiple modes of coupling occurs in Fig. 10. In (C), (D) and (F), parameter values in eqs. [5] and [6] (see Methods) are: Kice = 1 nM, Vdmce = 0.5 µM h−1, Kdmce = 0.5 µM, nce = 4, kce2 = 5 h−1. The strength of coupling through cyclin E is measured by the rate of synthesis of cyclin E mRNA depending on CLOCK-BMAL1, vsce. When multiple modes of coupling operate simultaneously, we multiply the rate of synthesis of Mw, Mp21, or Mce in eqs. [1]–[6] by the parameter μ, and put the value of vsw, vsmp21, or vsce equal to 1 µM h−1; μ then measures the strength of coupling to the circadian clock (see Methods where the various modes of coupling are detailed). The diagrams in (A) and (B) are the same as those of Fig. 4A and 8A, respectively; they are reproduced here to facilitate comparison with the other modes of entrainment.