The role played by MAD2L2 in the control of APC/C activation. As cells enter S phase, APC/C^CDH1, which has been active in G1, is inhibited by Emi1 and by degradation of CDH1. Emi1 can also inhibit newly produced CDC20 by sequestering it from the APC/C. Loss of APC/C activity results in Cyclin B1 stabilization and consequent phosphorylation of the APC/C, the activators CDC20 and CDH1 and of Emi1. Phosphorylated Emi1 is degraded via ubiquitination by the SCF^βTrCP. APC/C phosphorylation promotes binding of CDC20, but the complex is kept inactive by MAD2 and the mitotic checkpoint complex. Meanwhile, APC/C and CDH1 phosphorylation antagonizes activation of the APC/C by CDH1. CDH1 is additionally bound by MAD2L2, contributing to its sequestration away from the APC/C. Once the spindle assembly checkpoint (SAC) is satisfied and anaphase is initiated, APC/C^CDC20 degrades MAD2L2 and releases CDH1. CDH1 and the APC/C are also dephosphorylated, allowing CDH1 to bind and activate the APC/C. The sequestration of CDH1 by MAD2L2 acts to prevent premature activation of the APC/C by preventing binding of CDH1 to hypophosphorylated forms of the complex, thus ensuring the timing and bistability of the APC/C^CDC20 to APC/C^CDH1 switch. Model adapted from Pines, 2011.