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首页> 外文期刊>Nucleic Acids Research >hMSH5 is a nucleocytoplasmic shuttling protein whose stability depends on its subcellular localization
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hMSH5 is a nucleocytoplasmic shuttling protein whose stability depends on its subcellular localization

机译:hMSH5是一种核质穿梭蛋白,其稳定性取决于其亚细胞定位

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摘要

MSH5 is a MutS-homologous protein required for meiotic DNA recombination. In addition, recent studies suggest that the human MSH5 protein (hMSH5) participates to mitotic recombination and to the cellular response to DNA damage and thus raise the possibility that a tight control of hMSH5 function(s) may be important for genomic stability. With the aim to characterize mechanisms potentially involved in the regulation of hMSH5 activity, we investigated its intracellular trafficking properties. We demonstrate that hMSH5 possesses a CRM1-dependent nuclear export signal (NES) and a nuclear localization signal that participates to its nuclear targeting. Localization analysis of various mutated forms of hMSH5 by confocal microscopy indicates that hMSH5 shuttles between the nucleus and the cytoplasm. We also provide evidence suggesting that hMSH5 stability depends on its subcellular compartmentalization, hMSH5 being much less stable in the nucleus than in the cytoplasm. Together, these data suggest that hMSH5 activity may be regulated by nucleocytoplasmic shuttling and nuclear proteasomal degradation, both of these mechanisms contributing to the control of nuclear hMSH5 content. Moreover, data herein also support that in tissues where both hMSH5 and hMSH4 proteins are expressed, hMSH5 might be retained in the nucleus through masking of its NES by binding of hMSH4.
机译:MSH5是减数分裂DNA重组所需的MutS同源蛋白。此外,最近的研究表明,人MSH5蛋白(hMSH5)参与有丝分裂重组和细胞对DNA损伤的反应,因此提高了对hMSH5功能的严格控制对于基因组稳定性的重要性。为了表征可能参与hMSH5活性调节的机制,我们研究了其细胞内运输特性。我们证明,hMSH5拥有CRM1依赖性核出口信号(NES)和参与其核靶向的核定位信号。通过共聚焦显微镜对hMSH5的各种突变形式进行的定位分析表明,hMSH5在核和细胞质之间穿梭。我们还提供证据表明hMSH5的稳定性取决于其亚细胞区室化,hMSH5在细胞核中的稳定性远不如在细胞质中。在一起,这些数据表明,hMSH5活性可能受核质穿梭和核蛋白酶体降解的调节,这两种机制都有助于控制核hMSH5的含量。此外,本文的数据还支持在表达hMSH5和hMSH4蛋白的组织中,hMSH5可通过结合h​​MSH4掩盖其NES而被保留在细胞核中。

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