与人KPNA2（importin-α1）特异性结合并有效干扰核转运的适体,The Journal of Biochemistry

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与人KPNA2（importin-α1）特异性结合并有效干扰核转运的适体
The Journal of Biochemistry ( IF 2.1 ) Pub Date : 2016-05-06 , DOI: 10.1093/jb/mvw032
Noriko Yasuhara , Penmetcha K.R. Kumar

摘要importin-α蛋白家族在真核importin / exportin核转运系统中起着重要作用。这些蛋白质识别货物蛋白质中的核定位信号（NLS），并通过importin-β介导的过程将它们通过核孔导入核中。最近的研究表明，importin-α蛋白可以特异性识别几种细胞因子和病毒蛋白的NLS，从而调节其运动。Importin-α的失调是包括多种癌症在内的许多病理的共同特征。在这项研究中，我们分离了适体76和72，它们与导入素-α1的一个亚家族KPNA2特异性结合并有效结合。这两个适体均以150 nM的平衡解离常数（Kd）结合KPNA2，并区分KPNA2和importin-α的其他亚家族成员，例如KPNA1和KPNA3。这些适体专门干扰由KPNA2介导的货物蛋白的核转运，但既不干扰KPNA1也不影响KPNA3，KPNA3属于importins的其他亚家族。这些结果表明，选定的适体（76和72）值得进一步研究，以探索其在癌症诊断中的应用，以及它们作为一种特定试剂的用途，以潜在地阻止大分子KPNA2依赖性的大分子穿过核膜的核转运。属于importins的其他子家族。这些结果表明，选定的适体（76和72）值得进一步研究，以探索其在癌症诊断中的应用，以及它们作为一种特定试剂的用途，以潜在地阻止大分子KPNA2依赖性的大分子穿过核膜的核转运。属于importins的其他子家族。这些结果表明，选定的适体（76和72）值得进一步研究，以探索其在癌症诊断中的应用，以及它们作为一种特定试剂的用途，以潜在地阻止大分子KPNA2依赖性的大分子穿过核膜的核转运。

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Aptamers that bind specifically to human KPNA2 (importin-α1) and efficiently interfere with nuclear transport

Abstract The importin-α family of proteins plays an important role in the eukaryotic importin/exportin nuclear transport system. These proteins recognize a nuclear localization signal (NLS) within cargo proteins and import them into the nucleus through nuclear pores, in a process mediated by importin-β. Recent studies have shown that importin-α proteins specifically recognize the NLS of several cellular factors and viral proteins, thus regulating their movement. Dysregulation of importin-α is a common hallmark of many pathologies including, multiple cancers. In this study, we isolated aptamers 76 and 72, which bind specifically and efficiently to KPNA2, a member of a subfamily of importin-α1. Both of these aptamers bind to KPNA2 with an equilibrium dissociation constant (Kd) of 150 nM and discriminate between KPNA2 and other sub-family members of importin-α, such as KPNA1 and KPNA3. These aptamers specifically interfere with the nuclear transport of cargo proteins mediated by KPNA2 but neither with KPNA1 nor KPNA3, which belongs to other subfamily of importins. These results suggest that the selected aptamers (76 and 72) warrant further study to explore not only their application in cancer diagnosis but also their use as a specific reagent to potentially block KPNA2-dependent nuclear transport of macromolecules across the nuclear membrane.

更新日期：2016-05-06

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