Taming the Beast: Control of APC/CCdc20-Dependent Destruction

The anaphase-promoting complex/cyclosome (APC/C) is a large multisubunit ubiquitin ligase that triggers the metaphase-to-anaphase transition in the cell cycle by targeting the substrates cyclin B and securin for destruction. APC/C activity toward these two key substrates requires the coactivator Cdc20. To ensure that cells enter mitosis and partition their duplicated genome with high accuracy, APC/C Cdc20 activity must be tightly controlled. Here, we discuss the mechanisms that regulate APC/C Cdc20 activity both before and during mitosis. We focus our discussion primarily on the chromosomal pathways that both accelerate and delay APC/C activation by targeting Cdc20 to opposing fates. The findings discussed provide an overview of how cells control the activation of this major cell cycle regulator to ensure both accurate and timely cell division.