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Abstract：
Nuclear translocation of large proteins is mediated through specific protein carriers, collectively named karyopherins (importins, exportins and adaptor proteins). Cargo proteins are recognized by importins through specific motifs, known as nuclear localization signals (NLS). However, only the NLS recognized by importin α and transportin (M9 NLS) have been identified so far METHODS: An unsupervised in silico approach was used, followed by experimental validation.
We identified the sequence EKRKI(E/R)(K/L/R/S/T) as an NLS signal for importin 7 recognition. This sequence was validated in the breast cancer cell line T47D, which expresses importin 7. Finally, we verified that importin 7-mediated nuclear protein transport is affected by cargo protein phosphorylation.
The NLS sequence for importin 7 was identified and we propose this approach as an identification method of novel specific NLS sequences for β-karyopherin family members.
Elucidating the complex relationships of the nuclear transporters and their cargo proteins may help in laying the foundation for the development of novel therapeutics, targeting specific importins, with an immediate translational impact.
We identified the sequence EKRKI(E/R)(K/L/R/S/T) as an NLS signal for importin 7 recognition. This sequence was validated in the breast cancer cell line T47D, which expresses importin 7. Finally, we verified that importin 7-mediated nuclear protein transport is affected by cargo protein phosphorylation.
The NLS sequence for importin 7 was identified and we propose this approach as an identification method of novel specific NLS sequences for β-karyopherin family members.
Elucidating the complex relationships of the nuclear transporters and their cargo proteins may help in laying the foundation for the development of novel therapeutics, targeting specific importins, with an immediate translational impact.
摘要：
大蛋白质的核易位是通过特定的蛋白质载体介导的，统称为karyopherins(importins,出口蛋白和衔接蛋白）。货物蛋白通过特定的基序被进口蛋白识别，称为核定位信号(NLS)。然而,到目前为止，只有输入蛋白α和转运蛋白(M9NLS)识别的NLS被确定。方法：使用无监督的计算机模拟方法，其次是实验验证。
我们将序列EKRKI(E/R)(K/L/R/S/T)鉴定为用于导入蛋白7识别的NLS信号。该序列在乳腺癌细胞系T47D中得到验证，表达importin7.最后,我们验证了importin7介导的核蛋白转运受货物蛋白磷酸化的影响。
鉴定了importin7的NLS序列，我们提出了这种方法作为β-核蛋白家族成员的新型特异性NLS序列的鉴定方法。
阐明核转运蛋白及其货物蛋白的复杂关系可能有助于为新型疗法的开发奠定基础。针对特定的进口，立即产生翻译影响。
我们将序列EKRKI(E/R)(K/L/R/S/T)鉴定为用于导入蛋白7识别的NLS信号。该序列在乳腺癌细胞系T47D中得到验证，表达importin7.最后,我们验证了importin7介导的核蛋白转运受货物蛋白磷酸化的影响。
鉴定了importin7的NLS序列，我们提出了这种方法作为β-核蛋白家族成员的新型特异性NLS序列的鉴定方法。
阐明核转运蛋白及其货物蛋白的复杂关系可能有助于为新型疗法的开发奠定基础。针对特定的进口，立即产生翻译影响。
