The sequence [EKRKI(E/R)(K/L/R/S/T)] is a nuclear localization signal for importin 7 binding (NLS7).
Importin 7
Importin α
Importin β
Nuclear localization signal (NLS)
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
08
07
2020
revised:
14
01
2021
accepted:
14
01
2021
pubmed:
23
1
2021
medline:
30
6
2021
entrez:
22
1
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
RESULTS
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.
CONCLUSIONS
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.
GENERAL SIGNIFICANCE
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.
Identifiants
pubmed: 33482249
pii: S0304-4165(21)00010-6
doi: 10.1016/j.bbagen.2021.129851
pii:
doi:
Substances chimiques
IPO7 protein, human
0
Karyopherins
0
Nuclear Localization Signals
0
Receptors, Cytoplasmic and Nuclear
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
129851Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.