title: Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import.
abstract: 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.
authors.affiliation: Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lindsay
authors.forename: Kendra
authors.initials: K
authors.lastname: Plafker
authors.forename: Alicia E
authors.initials: AE
authors.lastname: Smith
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Clurman
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D002451:Cell Compartmentation / Q000502:physiology; D029563:Cellular Apoptosis Susceptibility Protein / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D015394:Molecular Structure; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D029563:Cellular Apoptosis Susceptibility Protein; D020690:GTPase-Activating Proteins; C424166:KPNB1 protein, human; D046911:Macromolecular Substances; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C092317:RANGAP1 protein, human; D028901:alpha Karyopherins; D028961:beta Karyopherins; C087978:karyopherin alpha 2; C091775:ran-binding protein 1; D020931:ran GTP-Binding Protein