Figure 1.

Schematic overview of the pathways that restrain APC/C activity post-translationally. The relative timing of their activation is generally shown.

The APC/C is most highly active from mid-mitosis and then throughout G1 phase. A schematic representation of the pathways that control APC/C and the degradation of its substrates during cell cycle progression is shown, with emphasis on those that operate outside of mitosis. Prior to metaphase, the activity of APC/C is prevented by the spindle assembly checkpoint, or SAC. The Cdc20-bound form is activated at metaphase (APC/C^Cdc20). In late mitosis, the Cdh1-bound form of APC/C becomes active (APC/C^Cdh1). The APC/C uses two E2 ubiquitin conjugating enzymes, UBE2C and UBE2S, which form K11-linked chains on substrates. The degradation of APC/C substrates is antagonized by the deubiquitinase Cezanne, which reverses K11-linked ubiquitin chains formed on APC/C substrates. The APC/C is then inactivated at G1/S through myriad mechanisms. The SCF^{Cyclin F} E3 ubiquitin ligase triggers Cdh1 degradation. The APC/C inhibitory protein EMI1 accumulates and binds APC/C. CDK2 phosphorylates Cdh1, preventing its binding to APC/C and promoting its cytoplasmic localization. The APC/C E2s are also degraded. A second ubiquitin ligase, SCF^βTRCP controls the destruction of Cdh1 and Emi1 later, and the degradation of both via this mechanisms is dependent on PLK1, which becomes active just prior to mitotic entry.