[PDF][PDF] PCBP1 suppresses the translation of metastasis-associated PRL-3 phosphatase
Cancer cell, 2010•cell.com
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 …
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 …
Summary
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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