Biology Department, Brooklyn College, The City University of New York, Brooklyn, NY 11238, USA.
Biology Program, CUNY Graduate Center, New York, NY 10016, USA.
J Cell Sci. 2020 Jul 29;133(14):jcs243766. doi: 10.1242/jcs.243766.
PP2A (the form of protein phosphatase 2A containing Cdc55) regulates cell cycle progression by reversing cyclin-dependent kinase (CDK)- and polo-like kinase (Cdc5)-dependent phosphorylation events. In , Cdk1 phosphorylates securin (Pds1), which facilitates Pds1 binding and inhibits separase (Esp1). During anaphase, Esp1 cleaves the cohesin subunit Scc1 and promotes spindle elongation. Here, we show that PP2A directly dephosphorylates Pds1 both and Pds1 hyperphosphorylation in a deletion mutant enhanced the Pds1-Esp1 interaction, which played a positive role in Pds1 nuclear accumulation and in spindle elongation. We also show that nuclear PP2A plays a role during replication stress to inhibit spindle elongation. This pathway acted independently of the known Mec1, Swe1 or spindle assembly checkpoint (SAC) checkpoint pathways. We propose a model where Pds1 dephosphorylation by PP2A disrupts the Pds1-Esp1 protein interaction and inhibits Pds1 nuclear accumulation, which prevents spindle elongation, a process that is elevated during replication stress.
蛋白磷酸酶 2A（包含 Cdc55 的蛋白磷酸酶 2A 形式）通过逆转细胞周期蛋白依赖性激酶 (CDK) 和 Polo 样激酶 (Cdc5) 依赖性磷酸化事件来调节细胞周期进程。在 中，Cdk1 磷酸化 securin（Pds1），这促进了 Pds1 与分离酶 (Esp1) 的结合并抑制其活性。在后期，Esp1 切割黏连蛋白亚基 Scc1 并促进纺锤体伸长。在这里，我们表明 PP2A 可直接去磷酸化 Pds1，无论是在 中还是在 缺失突变体中过度磷酸化 Pds1 都会增强 Pds1-Esp1 相互作用，这对 Pds1 的核积累和纺锤体伸长起到了积极作用。我们还表明，核内 PP2A 在复制应激期间发挥作用以抑制纺锤体伸长。该途径独立于已知的 Mek1、Swe1 或纺锤体组装检查点 (SAC) 检查点途径起作用。我们提出了一个模型，其中 PP2A 对 Pds1 的去磷酸化破坏了 Pds1-Esp1 蛋白相互作用并抑制了 Pds1 的核积累，从而阻止了纺锤体伸长，这一过程在复制应激期间会升高。
