Ki67 Antigen Contributes to the Timely Accumulation of Protein Phosphatase 1γ on Anaphase Chromosomes*
Ki67 Antigen Contributes to the Timely Accumulation of Protein Phosphatase 1γ on Anaphase Chromosomes*
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DOI：
10.1074/jbc.m114.556647
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发表时间：
2014-07
期刊：
影响因子：
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通讯作者：
M. Takagi;Yuko Nishiyama;Atsuko Taguchi;N. Imamoto
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文献类型：
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作者：
M. Takagi;Yuko Nishiyama;Atsuko Taguchi;N. Imamoto
背景：Ki 67是一种广泛使用的细胞增殖标志物，然而其细胞功能仍然是难以捉摸的。结果：Ki 67与蛋白磷酸酶1γ（PP 1 γ）相互作用，调节PP 1 γ在细胞分裂后期的定位。结论：Ki 67是一种新的PP 1 γ定位调节因子。意义：这项研究显示了一个新的例子，空间和时间控制后期染色体上的去磷酸化事件。Ki 67是一种被广泛用作细胞增殖标志物的蛋白质，其细胞功能尚不清楚。在本文中，我们提出了Ki 67和PP 1 γ之间的直接相互作用，PP 1 γ是一种蛋白磷酸酶，通过Ki 67内的经典PP 1结合基序在后期染色体上显示特征性积累。在Ki 67缺失的细胞中，PP 1 γ靶向后期染色体的效率较低。此外，Ki 67的过表达，而不是没有结合PP 1 γ能力的突变形式，诱导PP 1 γ在中期染色体上的异位定位。这些观察结果表明，Ki 67是决定PP 1 γ后期细胞行为的一个因素。为了探索通过与Ki 67相互作用在染色体上募集的PP 1 γ亚群（PP 1 γ-Ki 67）的特异性作用，用与PP 1 γ相互作用能力缺陷的Ki 67突变体替换内源性Ki 67。虽然在有丝分裂的进程中没有观察到明显的缺陷，但突变体Ki 67在后期的去磷酸化时间延迟，表明Ki 67本身是PP 1 γ-Ki 67的底物之一。
Background: Ki67 is a widely used cell proliferation marker whose cellular functions, however, remain elusive. Results: Ki67 interacts with protein phosphatase 1γ (PP1γ) and modulates its localization in anaphase. Conclusion: Ki67 is a novel regulator of PP1γ localization. Significance: This study shows a novel example of spatial and temporal control of dephosphorylation events on anaphase chromosomes. Ki67 is a protein widely used as cell-proliferation marker, with its cellular functions being hardly unveiled. In this paper, we present the direct interaction between Ki67 and PP1γ, a protein phosphatase showing characteristic accumulation on anaphase chromosomes via the canonical PP1-binding motif within Ki67. In cells depleted of Ki67, PP1γ is targeted to anaphase chromosomes less efficiently. Additionally, overexpression of Ki67, but not a mutant form without the ability to bind PP1γ, induced ectopic localization of PP1γ οn metaphase chromosomes. These observations demonstrate that Ki67 is one factor that defines the cellular behavior of PP1γ in anaphase. To explore the specific roles of the subset of PP1γ recruited on chromosome via its interaction with Ki67 (PP1γ-Ki67), endogenous Ki67 was replaced with a Ki67 mutant deficient in its ability to interact with PP1γ. Although no obvious defects in the progression of mitosis were observed, the timing of dephosphorylation of the mutant Ki67 in anaphase was delayed, indicating that Ki67 itself is one of the substrates of PP1γ-Ki67.