Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import.
Many nuclear-targeted proteins are transported through the nuclear pore complex (NPC) by the importin-alpha:beta receptor. We now show that Npap60 (also called Nup50), a protein previously believed to be a structural component of the NPC, is a Ran binding protein and a cofactor for importin-alpha:beta-mediated import. Npap60 is a tri-stable ... switch that alternates between binding modes. The C terminus binds importin-beta through RanGTP. The N terminus binds the C terminus of importin-alpha, while a central domain binds importin-beta. Npap60:importin-alpha:beta binds cargo and can stimulate nuclear import. Endogenous Npap60 can shuttle and is accessible from the cytoplasmic side of the nuclear envelope. These results identify Npap60 as a cofactor for importin-alpha:beta nuclear import and as a previously unidentified subunit of the importin complex.
Mesh Terms:
Active Transport, Cell Nucleus, Cell Compartmentation, Cellular Apoptosis Susceptibility Protein, Cytoplasm, Dimerization, Eukaryotic Cells, GTPase-Activating Proteins, Hela Cells, Humans, Macromolecular Substances, Molecular Structure, Nuclear Pore, Nuclear Pore Complex Proteins, Nuclear Proteins, Protein Binding, Protein Structure, Tertiary, Signal Transduction, alpha Karyopherins, beta Karyopherins, ran GTP-Binding Protein
Active Transport, Cell Nucleus, Cell Compartmentation, Cellular Apoptosis Susceptibility Protein, Cytoplasm, Dimerization, Eukaryotic Cells, GTPase-Activating Proteins, Hela Cells, Humans, Macromolecular Substances, Molecular Structure, Nuclear Pore, Nuclear Pore Complex Proteins, Nuclear Proteins, Protein Binding, Protein Structure, Tertiary, Signal Transduction, alpha Karyopherins, beta Karyopherins, ran GTP-Binding Protein
Cell
Date: Aug. 09, 2002
PubMed ID: 12176322
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