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蛋白磷酸酶 2A-SUR-6/B55 通过调控中心体组装因子的水平来调节线虫的中心体复制。

Protein phosphatase 2A-SUR-6/B55 regulates centriole duplication in C. elegans by controlling the levels of centriole assembly factors.

机构信息

Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Dev Cell. 2011 Apr 19;20(4):563-71. doi: 10.1016/j.devcel.2011.03.007.

Abstract

Centrioles play a crucial role in mitotic spindle assembly and duplicate precisely once per cell cycle. In worms, flies, and humans, centriole assembly is dependent upon a key regulatory kinase (ZYG-1/Sak/Plk4) and its downstream effectors SAS-5 and SAS-6. Here we report a role for protein phosphatase 2A (PP2A) in centriole duplication. We find that the PP2A catalytic subunit LET-92, the scaffolding subunit PAA-1, and the B55 regulatory subunit SUR-6 function together to positively regulate centriole assembly. In PP2A-SUR-6-depleted embryos, the levels of ZYG-1 and SAS-5 are reduced and the ZYG-1- and SAS-5-dependent recruitment of SAS-6 to the nascent centriole fails. We show that PP2A physically associates with SAS-5 in vivo and that inhibiting proteolysis can rescue SAS-5 levels and the centriole duplication defect of PP2A-depleted embryos. Together, our findings indicate that PP2A-SUR-6 promotes centriole assembly by protecting ZYG-1 and SAS-5 from degradation.

摘要

中心体在有丝分裂纺锤体组装中起着至关重要的作用,并且在细胞周期中精确复制一次。在蠕虫、苍蝇和人类中,中心体的组装依赖于关键调节激酶(ZYG-1/Sak/Plk4)及其下游效应物 SAS-5 和 SAS-6。在这里,我们报告了蛋白磷酸酶 2A(PP2A)在中心体复制中的作用。我们发现 PP2A 的催化亚基 LET-92、支架亚基 PAA-1 和 B55 调节亚基 SUR-6 共同正向调节中心体的组装。在 PP2A-SUR-6 耗尽的胚胎中,ZYG-1 和 SAS-5 的水平降低,并且 ZYG-1 和 SAS-5 依赖的 SAS-6 向新生中心体的募集失败。我们表明 PP2A 在体内与 SAS-5 物理结合,并且抑制蛋白水解可以挽救 PP2A 耗尽胚胎中 SAS-5 水平和中心体复制缺陷。总之,我们的发现表明 PP2A-SUR-6 通过保护 ZYG-1 和 SAS-5 免受降解来促进中心体的组装。

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