Bistability and hysteresis governing cyclin B–Cdk1 activity. The graph shows the theoretical relationship between cyclin B–Cdk1 concentration and cyclin B–Cdk1 activity. Note that the graph only shows steady-state end points and therefore does not contain any information on how much time is needed to reach the indicated activity. Because of the cyclin B–Cdk1–dependent feedback loops, the majority of cyclin B–Cdk1 complexes are either active, inactive, or approaching one of these states. A major determinant for whether cyclin B–Cdk1 will be active or inactive is the concentration of cyclin B–Cdk1 complexes; cyclin B–Cdk1 activation is triggered above a threshold concentration of cyclin B–Cdk1 complexes (red arrow). However, once the feedback loops are active, they can sustain cyclin B–Cdk1 activity at cyclin B–Cdk1 concentrations below the activation threshold. Therefore, the inactivation threshold is lower than the activation threshold (blue arrow). In this way, the feedback loops provide a resistance to change between the stable states. This resistance ensures that cyclin B–Cdk1 activity, and thereby the decision to enter or exit mitosis, is relatively insensitive to local fluctuations of mitotic entry network components.