Fig 2.

General function and key targets of the APC. The eukaryotic cell cycle is divided into four phases, mitosis (M), Gap1 (G₁), DNA synthesis (S), and Gap2 (G₂). The APC interacts with the coactivator Cdc20 or Cdh1 to form APC^Cdc20 or APC^Cdh1, respectively, the two of which act on different phases of the cell cycle. APC^Cdc20 starts to form toward the end of G₂ phase as CDK activity increases, but its activity is inhibited by the spindle assembly checkpoint (SAC) until anaphase. Once active, APC^Cdc20 degrades securin, cyclin B1, and others to promote the completion of M phase. APC^Cdc20 activity then diminishes in late M phase with the drop in CDK activity and degradation of Cdc20 by APC^Cdh1. In contrast, APC^Cdh1 is formed in late M phase and maintains high activity throughout G₁. It targets a number of proteins, including cyclin A2, geminin, ribonucleotide reductase (RRM2), thymidine kinase (TK), and others, for degradation to prevent premature entry into S phase. APC^Cdh1 must be inhibited before S phase can begin. It is inhibited by Emi1, CDK activity, and a negative feedback loop in which it targets Cdh1 for degradation.