Model of the effect of cyclin B–Cdk1 activity on cyclin B–Cdk1 nucleocytoplasmic shuttling. Once activated, cyclin B–Cdk1 autophosphorylates, thereby increasing its nuclear import. The nuclear import is most likely also affected by other components of the mitotic entry network. In the nucleus, Wee1 levels are high, leading to inactivation of the cyclin B–Cdk1 complex, which can no longer sustain the phosphorylation of cyclin B. After export to the cytoplasm, cyclin B–Cdk1 can be reactivated. Global activation of cyclin B–Cdk1 will occur when enough active cyclin B–Cdk1 enters the nucleus to promote Wee1 degradation, likely in cooperation with inhibitory phosphorylation of the cyclin B nuclear export sequence by an unknown kinase.