ArticleMolecular and cellular biology2017
RNA Binding Protein CUGBP1 Inhibits Liver Cancer in a Phosphorylation-Dependent Manner.
Article in Molecular and cellular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
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- Summary of biological research on hepatoblastoma: a scoping review.Frontiers in pediatrics · 2024Article
- Therapeutic Targeting of the GSK3β-CUGBP1 Pathway in Myotonic Dystrophy.International journal of molecular sciences · 2023Article
- CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis.International journal of molecular sciences · 2021Review
- Olaparib Inhibits Tumor Growth of Hepatoblastoma in Patient-Derived Xenograft Models.Hepatology (Baltimore, Md.) · 2021Article
- RNA binding protein CUGBP1 mediates the liver metastasis of colorectal cancer by regulating the ErbB signal pathway.Translational cancer research · 2021Article
- FAX-RIC enables robust profiling of dynamic RNP complex formation in multicellular organisms in vivo.Nucleic acids research · 2021Article
- Small Molecule Cjoc42 Improves Chemo-Sensitivity and Increases Levels of Tumor Suppressor Proteins in Hepatoblastoma Cells and in Mice by Inhibiting Oncogene Gankyrin.Frontiers in pharmacology · 2021Article
- Molecular signatures of aggressive pediatric liver cancer.Archives of stem cell and therapy · 2021Article
- Correction of Glycogen Synthase Kinase 3β in Myotonic Dystrophy 1 Reduces the Mutant RNA and Improves Postnatal Survival of DMSXL Mice.Molecular and cellular biology · 2019Article
- Liver Proliferation Is an Essential Driver of Fibrosis in Mouse Models of Nonalcoholic Fatty Liver Disease.Hepatology communications · 2019Article
- RNA Binding Proteins in Intestinal Epithelial Biology and Colorectal Cancer.Trends in molecular medicine · 2018Review
- PARP1 activation increases expression of modified tumor suppressors and pathways underlying development of aggressive hepatoblastoma.Communications biology · 2018Article
- Gankyrin Promotes Tumor-Suppressor Protein Degradation to Drive Hepatocyte Proliferation.Cellular and molecular gastroenterology and hepatology · 2018Article
- Probing the role of PPARγ in the regulation of late-onset Alzheimer's disease-associated genes.PloS one · 2018Article
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Authors and funding
10 authors at 2 institutions in 1 country.
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Abstract
Despite intensive investigations, mechanisms of liver cancer are not known. Here, we identified an important step of liver cancer, which is the neutralization of tumor suppressor activities of an RNA binding protein, CUGBP1. The translational activity of CUGBP1 is activated by dephosphorylation at Ser302. We generated CUGBP1-S302A knock-in mice and found that the reduction of translational activity of CUGBP1 causes development of a fatty liver phenotype in young S302A mice. Examination of liver cancer in diethylnitrosamine (DEN)-treated CUGBP1-S302A mice showed these mice develop much more severe liver cancer that is associated with elimination of the mutant CUGBP1. Searching for mechanisms of this elimination, we found that the oncoprotein gankyrin (Gank) preferentially binds to and triggers degradation of dephosphorylated CUGBP1 (de-ph-S302-CUGBP1) or S302A mutant CUGBP1. To test the role of Gank in degradation of CUGBP1, we generated mice with liver-specific deletion of Gank. In these mice, the tumor suppressor isoform of CUGBP1 is protected from Gank-mediated degradation. Consistent with reduction of CUGBP1 in animal models, CUGBP1 is reduced in patients with pediatric liver cancer. Thus, this work presents evidence that de-ph-S302-CUGBP1 is a tumor suppressor protein and that the Gank-UPS-mediated reduction of CUGBP1 is a key event in the development of liver cancer.
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