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NF-κB is transported into the nucleus by importin α3 and importin α4

Item Type:Article
Title:NF-κB is transported into the nucleus by importin α3 and importin α4
Creators Name:Fagerlund, R. and Kinnunen, L. and Koehler, M. and Julkunen, I. and Melen, K.
Abstract:NF-{kappa}B transcription factors are retained in the cytoplasm in an inactive form until they are activated and rapidly imported into the nucleus. We identified importin {alpha}3 and importin {alpha}4 as the main importin {alpha} isoforms mediating TNF-{alpha}-stimulated NF-{kappa}B p50/p65 heterodimer translocation into the nucleus. Importin {alpha}3 and {alpha}4 are close relatives in the human importin {alpha} family. We show that importin {alpha}3 isoform also mediates nuclear import of NF-{kappa}B p50 homodimer in nonstimulated cells. Importin {alpha}3 is shown to directly bind to previously characterized nuclear localization signals (NLSs) of NF-{kappa}B p50 and p65 proteins. Importin {alpha} molecules are known to have armadillo repeats that constitute the N-terminal and C-terminal NLS binding sites. We demonstrate by site-directed mutagenesis that NF-{kappa}B p50 binds to the N-terminal and p65 to the C-terminal NLS binding site of importin {alpha}3. In vitro competition experiments and analysis of cellular NF-{kappa}B suggest that NF-{kappa}B binds to importin {alpha} only when it is free of I{kappa}B{alpha}. The present study demonstrates that the nuclear import of NF-{kappa} is a highly regulated process mediated by a subset of importin {alpha} molecules.
Keywords:Alpha Karyopherins, Amino Acid Sequence, Cell Nucleus, Cultured Tumor Cells, I-{kappa} B Proteins, Kinetics, Molecular Sequence Data, NF-{kappa} B, Promoter Regions, Protein Transport, Site-Directed Mutagenesis, Tumor Necrosis Factor-alpha
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:280
Number:16
Page Range:15942-15951
Date:1 January 2005
Official Publication:https://doi.org/10.1074/jbc.M500814200
PubMed:View item in PubMed

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