title: The mammalian Mog1 protein is a guanine nucleotide release factor for Ran.
abstract: Ran is a Ras-related GTPase that is essential for the transport of protein and RNA between the nucleus and the cytoplasm. Proteins that regulate the GTPase cycle and subcellular distribution of Ran include the cytoplasmic GTPase-activating protein (RanGAP) and its co-factors (RanBP1, RanBP2), the nuclear guanine nucleotide exchange factor (RanGEF), and the Ran import receptor (NTF2). The recent identification of the Saccharomyces cerevisiae protein Mog1p as a suppressor of temperature-sensitive Ran mutations suggests that additional regulatory proteins remain to be characterized. Here, we describe the identification and biochemical characterization of murine Mog1, which, like its yeast orthologue, is a nuclear protein that binds specifically to RanGTP. We show that Mog1 stimulates the release of GTP from Ran, indicating that Mog1 functions as a guanine nucleotide release factor in vitro. Following GTP release, Mog1 remains bound to nucleotide-free Ran in a conformation that prevents rebinding of the guanine nucleotide. These properties distinguish Mog1 from the well characterized RanGEF and suggest an unanticipated mechanism for modulating nuclear levels of RanGTP.
authors.affiliation: Center for Cell Signaling, Department of Biochemistry and Molecular Genetics and the Cell and Molecular Biology Program, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Steggerda
authors.forename: B M
authors.initials: BM
authors.lastname: Paschal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C410219:MOG1 protein, S cerevisiase; D020931:ran GTP-Binding Protein