Molecular mechanisms of APC/C release from spindle assembly checkpoint inhibition by APC/C SUMOylation

Yatskevich, S.; Kroonen, J.S.; Alfieri, C.; Tischer, T.; Howes, A.C.; Clijsters, L.D.; ... ; Barford, D. (2021)

Article / Letter to editor

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the attachment of sister chromatids to the mitotic spindle. APC/C SUMOylation on APC4 ensures timely anaphase onset and chromosome segregation. To understand the structural and functional consequences of APC/C SUMOylation, we reconstituted SUMOylated APC/C for electron cryo-microscopy and biochemical analyses. SUMOylation of the APC/C causes a substantial rearrangement of the WHB domain of APC/C's cullin subunit (APC2(WHB)). Although APC/C-Cdc20 SUMOylation results in a modest impact on normal APC/C-Cdc20 activity, repositioning APC2(WHB) reduces the affinity of APC/C-Cdc20 for the mitotic checkpoint complex (MCC), the effector of the SAC. This attenuates MCC-mediated suppression of APC/C-Cdc20 activity, allowing for more efficient ubiquitination of APC/C-Cdc20 substrates in the presence of the MCC. Thus, SUMOylation stimulates the reactivation of APC/C-Cdc20 when the SAC is silenced, contributing to timely anaphase onset.

• All authors: Yatskevich, S.; Kroonen, J.S.; Alfieri, C.; Tischer, T.; Howes, A.C.; Clijsters, L.D.; Yang, J.; Zhang, Z.G.; Yan, K.G.; Vertegaal, A.C.O.; Barford, D.
• Date: 2021-03-30
• Journal: Cell Reports
• Volume: 34
• Issue: 13
• DOI: doi:10.1016/j.celrep.2021.108929
• Link: https://www.sciencedirect.com/science/article/pii/S2211124721002436?via%...