title: Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide exchange factor.
abstract: Ran-binding protein 3 (RanBP3) is an approximately 55-kDa protein that functions as a cofactor for Crm1-mediated nuclear export. RanBP3 stimulates export by enhancing the affinity of Crm1 for Ran.GTP and cargo. However, important additional functions for this cofactor may exist. We now report that RanBP3 associates with the Ran-specific guanine nucleotide exchange factor, regulator of chromosome condensation 1 (RCC1). This interaction was stimulated by the addition of Ran; moreover, Ran.GDP, Ran.GTP, and Ran without nucleotide could all stimulate complex formation between RanBP3 and RCC1 even though binding of Ran.GDP to RanBP3 alone was undetectable. RanBP3 could also promote binding of Crm1 to RCC1 in the presence of Ran. Binding of RanBP3 to RCC1 increased the catalytic activity of RCC1 toward Ran, and importantly, the ability of RanBP3 to stimulate RCC1 was not affected by the presence of Crm1. These data indicate that RanBP3 acts as a scaffold protein to promote the efficient assembly of export complexes. By tethering Crm1 to catalytically enhanced RCC1, RanBP3 may lower the entropic barrier for the loading of Ran.GTP onto Crm1. We propose that this provides an additional mechanism by which RanBP3 facilitates export.
authors.affiliation: Department of Microbiology, The Center for Cell Signaling, The University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Nemergut
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lindsay
authors.forename: Amy M
authors.initials: AM
authors.lastname: Brownawell
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
mesh_terms: D021581:Active Transport, Cell Nucleus; D002352:Carrier Proteins / Q000378:metabolism*; D020134:Catalytic Domain; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D046911:Macromolecular Substances; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D028884:Karyopherins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C112820:RANBP3 protein, human; C062521:RCC1 protein, human