Aptamers that bind specifically to human KPNA2 (importin-α1) and efficiently interfere with nuclear transport
| Autor: | Penmetcha K. R. Kumar, Noriko Yasuhara |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
alpha Karyopherins animal structures Aptamer importin-α Active Transport Cell Nucleus Importin nuclear transport Biology Biochemistry environment and public health 03 medical and health sciences 0302 clinical medicine medicine Humans Nuclear pore Nuclear membrane Molecular Biology Cancer Cell Nucleus Regular Papers Alpha Karyopherins General Medicine Aptamers Nucleotide Cell biology Cell nucleus 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures RNA Nuclear transport Nuclear localization sequence HeLa Cells |
| Zdroj: | Journal of Biochemistry |
| ISSN: | 1756-2651 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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