Cell Reports · 2012 · 156 citations · 34 references
Life SciencesCell BiologyMolecular BiologyGene ExpressionOncogenesProtein TranslationMrna ExportNuclear Pore ComplexesNuclear TransportRna ExportTranslation ControlTranslation RegulationEukaryotic Initiation Factor 2Eukaryotic Initiation Factor 4EMrna Export ComplexesMrna Export PathwaysMrna Nuclear ExportOncogenic TransformationProtein Nuclear ExportRna Export Factors
The eukaryotic translation initiation factor eIF4E is a potent oncogene that promotes the nuclear export and translation of specific transcripts. Here, we have discovered that eIF4E alters the cytoplasmic face of the nuclear pore complex (NPC), which leads to enhanced mRNA export of eIF4E target mRNAs. Specifically, eIF4E substantially reduces the major component of the cytoplasmic fibrils of the NPC, RanBP2, relocalizes an associated nucleoporin, Nup214, and elevates RanBP1 and the RNA export factors, Gle1 and DDX19. Genetic or pharmacological inhibition of eIF4E impedes these effects. RanBP2 overexpression specifically inhibits the eIF4E mRNA export pathway and impairs oncogenic transformation by eIF4E. The RanBP2 cytoplasmic fibrils most likely slow the release and/or recycling of critical export factors to the nucleus. eIF4E overcomes this inhibitory mechanism by indirectly reducing levels of RanBP2. More generally, these results suggest that reprogramming the NPC is a means by which oncogenes can harness the proliferative capacity of the cell.
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Roger L. Kaspar, Igor B. Rosenwald, Lee Gehrke et al. · Proceedings of the National Academy of Sciences · 1996 · 398 citations