Substrate targeting by the ubiquitin–proteasome system in mitosis

Both cell cycle progression and the ubiquitin–proteasome system (UPS) that drives it are precisely regulated. Enzymatically, many ubiquitylation and degradation reactions have been characterized in in vitro systems, providing insights into the fundamental mechanisms of the UPS. Biologically, a range of degradation events depending on a ubiquitin ligase called the Anaphase-Promoting Complex (APC/C), have been shown to control mitotic progression through removal of key substrates with extreme temporal precision. However we are only just beginning to understand how the different enzymatic activities of the UPS act collectively – and in cooperation with other cellular factors – for accurate temporal and spatial control of mitotic substrate levels in vivo.

► Mitosis progression relies on sequential destruction of key substrates.
► The ubiquitin–proteasome system targets these substrates with high temporal specificity.
► For most substrates, we do not understand how the specific timing of destruction is achieved.
► The APC/C ubiquitin ligase orchestrates ubiquitination of substrates.
► Other elements of the UPS may regulate the destruction of ubiquitinated substrates.