PCBP1 Suppresses the Translation of Metastasis-Associated PRL-3 Phosphatase Haihe Wang, Leah A. Vardy, Cheng Peow Tan, Jia Min Loo, Ke Guo, Jie Li, Seng Gee Lim, Jianbiao Zhou, Wee Joo Chng, Siok Bian Ng, Hui Xiang Li, Qi Zeng Cancer Cell - 13 July 2010 (Vol. 18, Issue 1, pp. 52-62)
Abstract:
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.