title: CUG-binding protein represses translation of p27Kip1 mRNA through its internal ribosomal entry site.
abstract: The cyclin dependent kinase inhibitor p27 (Kip1) plays an important role in controlling the eukaryotic cell cycle. The 5'-untranslated region of the p27 mRNA harbors an internal ribosome entry site (IRES) which may facilitate synthesis of p27 in certain conditions. In this study, the RNA-associated protein CUGBP1 was shown to interact with the human p27 5'-untranslated region. Overexpression of CUGBP1 inhibited endogenous p27 expression and reduced translation initiation through the p27 IRES. In contrast, repression of CUGBP1 by siRNA transfection enhanced p27 protein levels and stimulated p27 IRES activity. Addition of recombinant CUGBP1 repressed p27 IRES reporter mRNA translation in vitro. At last, Our finding showed that cytosolic form of CUGBP1 binds efficiently to the p27 5'-untranslated region.
authors.affiliation: Cancer Biology Research Center, Sanford Research/USD, Sioux Falls, and Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, SD, USA. yuzheng@mdanderson.org
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Zheng
authors.forename: W Keith
authors.initials: WK
authors.lastname: Miskimins
mesh_terms: D020121:5' Untranslated Regions; D001665:Binding Sites; D000067879:CELF1 Protein; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D014162:Transfection
chemical_list: D020121:5' Untranslated Regions; D000067879:CELF1 Protein; C102843:CELF1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27