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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding
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Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding

机译：在细胞周期蛋白A中发现一个独立的结构域，足以独立于Cdk结合进行中心体定位

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摘要

Centrosomes have recently emerged as key regulators of the cell cycle. The G1/S transition requires a functional centrosome, and centrosomal localization of numerous proteins, including cyclin/Cdk complexes, is important for the G2/M transition. Here we identify a modular centrosomal localization signal (CLS) localizing cyclin A to centrosomes independently of Cdk binding. The cyclin A CLS is located in a distinct part of the molecule compared with the cyclin E CLS and includes the MRAIL hydrophobic patch involved in substrate recognition. The cyclin A CLS interacts with p27~(KIP1), and expression of p27~(KIP1) removes cyclin A but not cyclin E from centrosomes. Expression of the cyclin A CLS displaces both endogenous cyclin A and E from centrosomes and inhibits DNA replication, supporting an emerging concept that DNA replication is linked to centrosomal events. Structural analysis indicates that differences in surface charge and length of the C-terminal helix explain why the MRAIL region in cyclin E is not a functional CLS. These results indicate that the cyclin A CLS may contribute to targeting and recognition of centrosomal Cdk substrates and is required for specific effects of p27~(KIP1) on cyclin A-Cdk2.
机译：中心体最近已成为细胞周期的关键调控因子。 G1 / S过渡需要有功能的中心体，许多蛋白质（包括细胞周期蛋白/ Cdk复合物）的中心体定位对于G2 / M过渡很重要。在这里，我们确定独立于Cdk绑定的模块化中心体定位信号（CLS）将细胞周期蛋白A定位到中心体。与细胞周期蛋白E CLS相比，细胞周期蛋白A CLS位于分子的不同部分，并且包括参与底物识别的MRAIL疏水膜片。细胞周期蛋白A CLS与p27〜（KIP1）相互作用，而p27〜（KIP1）的表达可从中心体中去除细胞周期蛋白A，但不会去除细胞周期蛋白E。细胞周期蛋白A CLS的表达可将内源性细胞周期蛋白A和E从中心体中移出并抑制DNA复制，从而支持了DNA复制与中心体事件相关的新兴概念。结构分析表明，表面电荷和C末端螺旋长度的差异解释了为什么细胞周期蛋白E中的MRAIL区不是功能性CLS。这些结果表明细胞周期蛋白A CLS可能有助于靶向和识别中心体Cdk底物，是p27〜（KIP1）对细胞周期蛋白A-Cdk2产生特定作用所必需的。

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