%0 Journal Article
%T CDK1-PP2A-B55 interplay ensures cell cycle oscillation via Apc1-loop300.
%A Chia KH
%A Takaki H
%A Fujimitsu K
%A Darling S
%A Zou J
%A Rappsilber J
%A Yamano H
%J Cell Rep
%V 43
%N 5
%D 2024 May 28
%M 38678563
暂无%R 10.1016/j.celrep.2024.114155
%X 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.