Chia, Kim Hou;
Takaki, Hiroko;
Fujimitsu, Kazuyuki;
Darling, Sarah;
Zou, Juan;
Rappsilber, Juri;
Yamano, Hiroyuki;
(2024)
CDK1-PP2A-B55 interplay ensures cell cycle oscillation via Apc1-loop300.
Cell Reports
, 43
(5)
, Article 114155. 10.1016/j.celrep.2024.114155.
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Abstract
Cell cycle control relies on a delicate balance of phosphorylation with CDK1 and phosphatases like PP1 and PP2A-B55. Yet, identifying the primary substrate responsible for cell cycle oscillations remains a challenge. We uncover the pivotal role of phospho-regulation in the anaphase-promoting complex/cyclosome (APC/C), particularly through the Apc1-loop300 domain (Apc1-300L), orchestrated by CDK1 and PP2A-B55. Premature activation of PP2A-B55 during mitosis, induced by Greatwall kinase depletion, leads to Apc1-300L dephosphorylation, stalling APC/C activity and delaying Cyclin B degradation. This effect can be counteracted using the B55-specific inhibitor pEnsa or by removing Apc1-300L. We also show Cdc20's dynamic APC/C interaction across cell cycle stages, but dephosphorylation of Apc1-300L specifically inhibits further Cdc20 recruitment. Our study underscores APC/C's central role in cell cycle oscillation, identifying it as a primary substrate regulated by the CDK-PP2A partnership.
| Type: | Article |
|---|---|
| Title: | CDK1-PP2A-B55 interplay ensures cell cycle oscillation via Apc1-loop300 |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2024.114155 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2024.114155 |
| Language: | English |
| Additional information: | © 2024 Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
| Keywords: | APC/C, CDK, CP: Cell biology, CP: Molecular biology, Cdc20, Cell cycle, PP2A-B55, intrinsically disordered regions, mitosis, phosphatase, phosphorylation, ubiquitin ligase |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10191574 |
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