Centre de Recherche de Biologie cellulaire de Montpellier (CRBM), CNRS UMR 5237, Université de Montpellier, 1919 Route de Mende, 34293 Montpellier cedex 5, France
J Cell Sci. 2018 Oct 24;131(20):jcs222364. doi: 10.1242/jcs.222364.
Mitosis is controlled by a subtle balance between kinase and phosphatase activities that involve the master mitotic kinase cyclin-B-Cdk1 and its antagonizing protein phosphatase 2A-B55 (PP2A-B55). Importantly, the Greatwall (Gwl; known as Mastl in mammals, Rim15 in budding yeast and Ppk18 in fission yeast) kinase pathway regulates PP2A-B55 activity by phosphorylating two proteins, cAMP-regulated phosphoprotein 19 (Arpp19) and α-endosulfine (ENSA). This phosphorylation turns these proteins into potent inhibitors of PP2A-B55, thereby promoting a correct timing and progression of mitosis. In this Cell Science at a Glance article and the accompanying poster, we discuss how Gwl is regulated in space and time, and how the Gwl-Arpp19-ENSA-PP2A-B55 pathway plays an essential role in the control of M and S phases from yeast to human. We also summarize how Gwl modulates oncogenic properties of cells and how nutrient deprivation influences Gwl activity.
有丝分裂由激酶和磷酸酶活性之间的微妙平衡控制，其中涉及主有丝分裂激酶 cyclin-B-Cdk1 及其拮抗蛋白磷酸酶 2A-B55（PP2A-B55）。重要的是，壁（Gwl；在哺乳动物中称为 Mastl，在芽殖酵母中称为 Rim15，在裂殖酵母中称为 Ppk18）激酶途径通过磷酸化两种蛋白质 cAMP 调节磷酸蛋白 19（Arpp19）和 α-内磺素（ENSA）来调节 PP2A-B55 的活性。这种磷酸化使这些蛋白质成为 PP2A-B55 的有效抑制剂，从而促进有丝分裂的正确时间和进程。在这篇《细胞科学概览》文章及其配套海报中，我们讨论了 Gwl 如何在空间和时间上受到调节，以及 Gwl-Arpp19-ENSA-PP2A-B55 途径如何在从酵母到人类的 M 和 S 期控制中发挥重要作用。我们还总结了 Gwl 如何调节细胞的致癌特性以及营养物质缺乏如何影响 Gwl 活性。
