High impact information on MOG1

• Consistent with the high efficiency of gsp1 suppression, Mog1p directly bound to GTP, but not to GDP-Gsp1p [1].
• Thus, Mog1p, which was localized in the nucleus, is a Gsp1p-binding protein involved in nuclear-protein import and that functionally interacts with Ntf2p [1].
• Moreover, MOG1 shows synthetic lethality with PRP20, the Ran guanine nucleotide exchange factor (RanGEF) that also binds nucleotide-free Ran [2].
• Mog1 is a nuclear protein that interacts with Ran, the Ras family GTPase that confers directionality to nuclear import and export pathways [2].
• Furthermore, the E65K-Mog1 and K136E-Ran mutations in yeast cause temperature sensitivity and mislocalization of a nuclear import reporter protein, similar to the phenotype observed for the Deltamog1 strain [2].

Biological context of MOG1

• Taken together, our findings suggest that MOG1 is an evolutionarily conserved Ran binding protein that could play a role in regulating nuclear protein trafficking [3].
• Mog1p binds the Ras-family GTPase Ran/Gsp1p, which has a central role in nucleocytoplasmic transport and cell-cycle progression [4].
• In contrast to the S. cerevisiae MOG1 gene, the S. pombe mog1(+) gene is essential for cell viability. mog1(+) is required for the mitosis-to-interphase transition, as the mog1-1 mutant arrests at restrictive temperatures as septated, binucleated cells with highly condensed chromosomes and an aberrant nuclear envelope [5].
• By screening a Xenopus oocyte cDNA library for Ran-GTP-binding proteins using the two-hybrid system of co-expression in yeast, we identified XMog1, a 20.4 kDa polypeptide related to Mog1p in Saccharomyces cerevisiae and similar gene products in Schizosaccharomyces pombe, Arabidopsis and mammals [6].
• Although there may be some overlap between the Mog1p and NTF2 binding sites on RanGDP, these sites are not identical [7].

Regulatory relationships of MOG1

• Overexpression of MOG1 is able to suppress temperature-sensitive gsp1 mutants in yeast; Deltamog1 null mutants display temperature-sensitive defects in nuclear trafficking [4].
• At a concentration corresponding to the molar concentration of GTP-Gsp1p, Yrb1p completely inhibited the Mog1p-stimulated nucleotide release [8].

Other interactions of MOG1

• A protein required for nuclear-protein import, Mog1p, directly interacts with GTP-Gsp1p, the Saccharomyces cerevisiae ran homologue [1].
• Yrb1p did not inhibit the Mog1p-stimulated nucleotide release from GTP-Gsp1DeltaC [8].
• We found that overexpression of Spi1p rescues the S. pombe Delta mog1 cells from death [5].
• Surprisingly, also unlike the Delta mog1 mutation in S. cerevisiae, the mog1-1 mutation causes nucleolar accumulation of poly(A)(+) RNA at the restrictive temperature in S. pombe, but the signals do not overlap with the fibrillarin-rich region of the nucleolus [5].

Analytical, diagnostic and therapeutic context of MOG1

• Crystallization and preliminary X-ray diffraction analysis of the Saccharomyces cerevisiae ran-binding protein Mog1p [4].
• Sequence analysis of Mog1p homologues from Schizosaccharomyces pombe, human, and Caenorhabditis elegans in the context of the Mog1p crystal structure indicates the presence of a cluster of highly conserved surface residues consistent with an interaction site for Ran [7].

References