A Model of Yeast Cell-Cycle Regulation Based on a Standard Component Modeling Strategy for Protein Regulatory Networks
Fig 9
Simulations of wild-type cells.
(A) Start: As the cell grows (increasing Vn), Cln3 accumulates and phosphorylates Whi5. At a critical cell size, SBF is abruptly released from the inactive SBF:Whi5 complex and initiates a positive feedback loop between the accumulation of Cln2 and the phosphorylation of Whi5. (B) G1/S/G2/M: SBF also promotes the synthesis of Clb5. Once Clb5 titrates out CKI, then Clb5 and Cln2 together inactivate Cdh1, resulting in the accumulation of Clb2. Exit: Clb2 triggers many mitotic events, eventually leading to the release of Cdc14 during mitotic exit. When Clb2 drops below a normalized concentration of 0.4, the cell divides asymmetrically between daughter and mother cells. The daughter cell receives 42% of the cell size at division, and the mother cell (not shown here) receives the remaining 58%. (C and D) The stochastic model shows the typical fluctuations of protein concentrations around the average dynamics predicted by the corresponding deterministic model. For easier comparison to the deterministic simulation (A and B), we converted the numbers of molecules reported by the stochastic simulation to normalized concentrations. Start and division events are indicated by up-pointing and down-pointing black triangles, respectively.