Negative feedback regulation of the signal pathways. I. The protein amounts and reaction probabilities were set as described in Additional file 1 and 2, respectively. L was added immediately before the 1.2 × 106th step (down arrow, 24 seconds) and removed after the 1.2 × 107th step (upper allow, 240 seconds), as described in the legend of Figure 2. Three simulation results are represented. II. Models for negative feedback regulation used in this study.