Cell Reports · 2021 · 68 citations · 26 references
Life SciencesMolecular BiologyOncologyCancer GeneticsGene ExpressionMolecular OncologyCancer Cell SignalingPost-translational RegulationProtein SynthesisSignal Transduction In CancerTranslation RegulationTranslational Regulation3' Untranslated Region RegulationAu-rich Element Binding ProteinsEukaryotic Initiation FactorsEukaryotic Translation Initiation FactorsReverse-phase Protein MicroarraysRna Binding Protein RegulationRna-binding Protein Regulation Of TranslationTranslational Control In Cancer
Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3' untranslated region (3'UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover a mechanism by which FXR1 promotes cMYC levels in cancer cells.
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The Molecular Signatures Database Hallmark Gene Set Collection
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