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首页> 外文期刊>Molecular and Cellular Biology >PR48, a Novel Regulatory Subunit of Protein Phosphatase 2A, Interacts with Cdc6 and Modulates DNA Replication in Human Cells
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PR48, a Novel Regulatory Subunit of Protein Phosphatase 2A, Interacts with Cdc6 and Modulates DNA Replication in Human Cells

机译：PR48，蛋白磷酸酶2A的新型调节亚基，与Cdc6相互作用并调节人细胞中的DNA复制

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摘要

Initiation of DNA replication in eukaryotes is dependent on the activity of protein phosphatase 2A (PP2A), but specific phosphoprotein substrates pertinent to this requirement have not been identified. A novel regulatory subunit of PP2A, termed PR48, was identified by a yeast two-hybrid screen of a human placental cDNA library, using human Cdc6, an essential component of prereplicative complexes, as bait. PR48 binds specifically to an amino-terminal segment of Cdc6 and forms functional holoenzyme complexes with A and C subunits of PP2A. PR48 localizes to the nucleus of mammalian cells, and its forced overexpression perturbs cell cycle progression, causing a G1 arrest. These results suggest that dephosphorylation of Cdc6 by PP2A, mediated by a specific interaction with PR48, is a regulatory event controlling initiation of DNA replication in mammalian cells.
机译：真核生物中DNA复制的启动取决于蛋白磷酸酶2A（PP2A）的活性，但尚未确定与该要求有关的特定磷蛋白底物。 PP2A的新型调节亚基，称为PR48，是通过人胎盘cDNA文库的酵母双杂交筛选而鉴定的，其中使用了复制前复合物的必需成分人Cdc6作为诱饵。 PR48与Cdc6的氨基末端片段特异性结合，并与PP2A的A和C亚基形成功能性全酶复合物。 PR48定位于哺乳动物细胞核，其被强迫的过度表达扰乱了细胞周期进程，导致G 1 停滞。这些结果表明，通过与PR48的特异性相互作用介导的PP2A对Cdc6的去磷酸化是控制哺乳动物细胞中DNA复制起始的调节事件。

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