PCBP1 Suppresses the Translation of Metastasis-Associated PRL-3 Phosphatase
Copyright policy )PCBP1 Suppresses the Translation of Metastasis-Associated PRL-3 Phosphatase
Overexpression of phosphatase of regenerating liver (PRL)-3 is associated with the progression of diverse human cancers. We show that the overexpression of PRL-3 protein is not directly associated with its transcript levels, indicating the existence of an underlying posttranscriptional regulation. The 5' untranslanted region (UTR) of PRL-3 mRNA possesses triple GCCCAG motifs capable of suppressing mRNA translation through interaction with PolyC-RNA-binding protein 1 (PCBP1), which retards PRL-3 mRNA transcript incorporation into polyribosomes. Overexpression of PCBP1 inhibits PRL-3 expression and inactivates AKT, whereas knockdown of PCBP1 causes upregulation of PRL-3 protein levels, activation of AKT, and promotion of tumorigenesis. An inverse correlation between protein levels of PRL-3 and PCBP1 in human primary cancers supports the clinical relevance.
- Rockefeller University United States
- University Health System United States
- Institute of Medical Virology Switzerland
- National University Cancer Institute Singapore
- Nationl University of Singapore Singapore
EXPRESSION, Cancer Research, LIVER METASTASIS, 572, MIGRATION, INVASION, Blotting, Western, Mice, Nude, Electrophoretic Mobility Shift Assay, CELLCYCLE, Heterogeneous-Nuclear Ribonucleoproteins, COLORECTAL-CANCER, Immunoenzyme Techniques, Mice, MOTILITY, Cell Line, Tumor, Neoplasms, ERYTHROID-DIFFERENTIATION, Animals, Humans, Neoplasm Metastasis, Luciferases, Promoter Regions, Genetic, Science & Technology, Cell Biology, PROTEIN-TYROSINE PHOSPHATASES, Neoplasm Proteins, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Oncology, Lymphatic Metastasis, Polyribosomes, Protein Biosynthesis, OVEREXPRESSION, MESSENGER-RNA, 5' Untranslated Regions, Life Sciences & Biomedicine
EXPRESSION, Cancer Research, LIVER METASTASIS, 572, MIGRATION, INVASION, Blotting, Western, Mice, Nude, Electrophoretic Mobility Shift Assay, CELLCYCLE, Heterogeneous-Nuclear Ribonucleoproteins, COLORECTAL-CANCER, Immunoenzyme Techniques, Mice, MOTILITY, Cell Line, Tumor, Neoplasms, ERYTHROID-DIFFERENTIATION, Animals, Humans, Neoplasm Metastasis, Luciferases, Promoter Regions, Genetic, Science & Technology, Cell Biology, PROTEIN-TYROSINE PHOSPHATASES, Neoplasm Proteins, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Oncology, Lymphatic Metastasis, Polyribosomes, Protein Biosynthesis, OVEREXPRESSION, MESSENGER-RNA, 5' Untranslated Regions, Life Sciences & Biomedicine
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