Motifs targeted by APC/C

The anaphase- promoting complex or cyclosome (APC/C) is a highly specific ubiquitin protein ligase responsible for triggering events of late mitosis. In early mitosis, Cdc20 levels rise and APC/C binds to form active APC/CCdc20. This then leads to the destruction of mitotic cyclins, securin, and other proteins to trigger chromosome separation in anaphase.^[1] In early anaphase, Cdk1 is inactivated, leading to the activation of Cdh1, the other activator subunit of APC/C. This then triggers the degradation of Cdc20 and leads to the activation of APC/CCdh1 through G1 to suppress S- phase cyclin-Cdk activity. At the end of G1, APC/CCdh1 is inactivated and S- phase and mitotic cyclins gets reaccumulate as the cell progresses to S phase.^[1]

APC/C finds its substrates via short, linear sequence motifs or degrons found in its substrates. These degrons can be split into three major groups: destruction boxes, KEN boxes, and ABBA motifs.^[1] Binding pockets on the surface of activator subunits of Cdc20 or Cdh1 interact with the degrons on the substrates to target them for ubiquitination and degradation to trigger specific events in the cell cycle.^[1]