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.
摘要：
细胞周期控制依赖于CDK1和磷酸酶如PP1和PP2A-B55的磷酸化的微妙平衡。然而，确定导致细胞周期振荡的主要底物仍然是一个挑战。我们揭示了磷酸调节在后期促进复合物/环小体（APC/C）中的关键作用，特别是通过Apc1-loop300域（Apc1-300L），由CDK1和PP2A-B55协调。PP2A-B55在有丝分裂过程中过早激活，由Greatwall激酶耗竭诱导，导致Apc1-300L去磷酸化，停止APC/C活性和延迟细胞周期蛋白B降解。可以使用B55特异性抑制剂pEnsa或通过去除Apcl-300L来抵消这种作用。我们还显示了Cdc20在细胞周期阶段的动态APC/C相互作用，但是Apc1-300L的去磷酸化特异性地抑制了Cdc20的进一步募集。我们的研究强调了APC/C在细胞周期振荡中的核心作用，将其鉴定为受CDK-PP2A伙伴关系调节的主要底物。
