Department of Biology, Brandeis University, Waltham, MA 02454, USA.
J Cell Biol. 2011 May 2;193(3):445-54. doi: 10.1083/jcb.201101134.
Budding yeast CDC55 encodes a regulatory B subunit of the PP2A (protein phosphatase 2A), which plays important roles in mitotic entry and mitotic exit. The spatial and temporal regulation of PP2A is poorly understood, although recent studies demonstrated that the conserved proteins Zds1 and Zds2 stoichiometrically bind to Cdc55-PP2A and regulate it in a complex manner. Zds1/Zds2 promote Cdc55-PP2A function for mitotic entry, whereas Zds1/Zds2 inhibit Cdc55-PP2A function during mitotic exit. In this paper, we propose that Zds1/Zds2 primarily control Cdc55 localization. Cortical and cytoplasmic localization of Cdc55 requires Zds1/Zds2, and Cdc55 accumulates in the nucleus in the absence of Zds1/Zds2. By genetically manipulating the nucleocytoplasmic distribution of Cdc55, we showed that Cdc55 promotes mitotic entry when in the cytoplasm. On the other hand, nuclear Cdc55 prevents mitotic exit. Our analysis defines the long-sought molecular function for the zillion different screens family proteins and reveals the importance of the regulation of PP2A localization for proper mitotic progression.
芽殖酵母 CDC55 编码蛋白磷酸酶 2A（PP2A）的调节 B 亚基，在有丝分裂进入和有丝分裂退出中发挥重要作用。尽管最近的研究表明，保守蛋白 Zds1 和 Zds2 以化学计量的方式结合到 Cdc55-PP2A 并以复杂的方式调节它，但 PP2A 的时空调节仍知之甚少。Zds1/Zds2 促进 Cdc55-PP2A 在有丝分裂进入中的功能，而 Zds1/Zds2 在有丝分裂退出期间抑制 Cdc55-PP2A 的功能。在本文中，我们提出 Zds1/Zds2 主要控制 Cdc55 的定位。Cdc55 的皮质和细胞质定位需要 Zds1/Zds2，并且在没有 Zds1/Zds2 的情况下，Cdc55 在核内积累。通过遗传操纵 Cdc55 的核质分布，我们表明细胞质中的 Cdc55 促进有丝分裂进入。另一方面，核 Cdc55 阻止有丝分裂退出。我们的分析定义了 zillion 不同筛选家族蛋白长期以来寻求的分子功能，并揭示了适当的有丝分裂进展中 PP2A 定位调节的重要性。
