title: The nucleoporin Nup358/RanBP2 promotes nuclear import in a cargo- and transport receptor-specific manner.
abstract: In vertebrates, the nuclear pore complex (NPC), the gate for transport of macromolecules between the nucleus and the cytoplasm, consists of approximately 30 different nucleoporins (Nups). The Nup and SUMO E3-ligase Nup358/RanBP2 are the major components of the cytoplasmic filaments of the NPC. In this study, we perform a structure-function analysis of Nup358 and describe its role in nuclear import of specific proteins. In a screen for nuclear proteins that accumulate in the cytoplasm upon Nup358 depletion, we identified proteins that were able to interact with Nup358 in a receptor-independent manner. These included the importin α/β-cargo DBC-1 (deleted in breast cancer 1) and DMAP-1 (DNA methyltransferase 1 associated protein 1). Strikingly, a short N-terminal fragment of Nup358 was sufficient to promote import of DBC-1, whereas DMAP-1 required a larger portion of Nup358 for stimulated import. Neither the interaction of RanGAP with Nup358 nor its SUMO-E3 ligase activity was required for nuclear import of all tested cargos. Together, Nup358 functions as a cargo- and receptor-specific assembly platform, increasing the efficiency of nuclear import of proteins through various mechanisms.
authors: Department of Biochemistry I, Faculty of Medicine, Georg-August-University of Göttingen, Humboldtallee 23, 37073, Göttingen, Germany.
authors: Sarah
authors: S
authors: Wälde
authors: Ketan
authors: K
authors: Thakar
authors: Saskia
authors: S
authors: Hutten
authors: Christiane
authors: C
authors: Spillner
authors: Annegret
authors: A
authors: Nath
authors: Ulrich
authors: U
authors: Rothbauer
authors: Stefan
authors: S
authors: Wiemann
authors: Ralph H
authors: RH
authors: Kehlenbach
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000502:physiology; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000378:metabolism; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human; C411744:DMAP1 protein, human; D028884:Karyopherins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D019913:Nuclear Localization Signals; D028861:Nuclear Pore Complex Proteins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; D028901:alpha Karyopherins; D028961:beta Karyopherins; C094493:ran-binding protein 2; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; C412324:DDX43 protein, human; D053487:DEAD-box RNA Helicases