Fig. 4

APC/C in cell cycle regulation. The regulation of APC/C activity and the order degradation of APC/C substrates during cell cycle progression. Regulation of cell cycle progression by the APC/C occurs primarily through the temporal coordination of Cdc20 or Cdh1. APC/C–Cdc20 degrades substrates in early and mid-mitosis, while APC/C–Cdh1 degrades substrates after anaphase commencement, during the end of mitosis and G1 phase. During G2/M transition phase, APC/C–Cdc20 is activated by CDK1 phosphorylation, whereas is inhibited by spindle assembly checkpoint (SAC) and mitotic checkpoint complex (MCC). When checkpoint requirement is satisfied, APC/C–Cdc20 ubiquitylates Cyclin-A, NEK2A in prometaphase and securin and cyclin B1 in metaphase. When cell commences to anaphase, Cdh1 is dephosphorylated by CDC14 and activates APC/C–Cdh1. During anaphase and telophase, APC/C–Cdh1 ubiquitylates substrates including Cdc20, Aurora kinases, PLK1, TPX2, spindle-binding proteins and stress-activated kinases. During G1 phase, APC/C–Cdh1 degrades mitotic cyclins such as Cdc25A, Skp2. During G1/S transition and G2 phase, APC/C–Cdh1 is inactivated by Emi1, Cdh1 degradation, phosphorylation by Cyclin A/Cdk2 and degradation of E2s