18.18 : Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and activates it, resulting in the formation of APC^Cdc20 and APC^Cdh1 complexes, respectively. Cdc20 and Cdh1 also help APC to identify its substrates.

APC^Cdc20 plays an essential role in metaphase to anaphase transition. The sister chromatids are held together by cohesins. The cohesin rings need to be broken by the enzyme separase so that the sister chromatids can move towards the opposite poles during anaphase. However, separase activity is inhibited by the protein, securin. APC^Cdc20 ubiquitinates securin, leading to its proteasomal degradation. This leads to the subsequent activation of the separase. APC^Cdc20 also ubiquitinates mitotic cyclins, which in turn inactivates cyclin-dependent kinases or Cdks. The inactivation of Cdks and the subsequent dephosphorylation of Cdk-substrates are necessary for the completion of cell division.