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.
Wang
Haihe
H
Institute of Molecular and Cell Biology, A*Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos, Singapore 138648, Republic of Singapore.
Vardy
Leah A
LA
Tan
Cheng Peow
CP
Loo
Jia Min
JM
Guo
Ke
K
Li
Jie
J
Lim
Seng Gee
SG
Zhou
Jianbiao
J
Chng
Wee Joo
WJ
Ng
Siok Bian
SB
Li
Hui Xiang
HX
Zeng
Qi
Q
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011132:Polyribosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009363:Neoplasm Proteins; C094604:PCBP1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D008156:Luciferases; D051057:Proto-Oncogene Proteins c-akt; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases