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Cancer Cell. 2010 Jul 13;18(1):52-62. doi: 10.1016/j.ccr.2010.04.028.

PCBP1 suppresses the translation of metastasis-associated PRL-3 phosphatase.

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Institute of Molecular and Cell Biology, A*Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos, Singapore 138648, Republic of Singapore.


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.

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