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(Journal Article) |
Cancer cell 18 (1): 52-62 (2010)
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
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.