title: CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation.
abstract: The cytoplasmic element binding protein 1 (CPEB1) regulates many important biological processes ranging from cell cycle control to learning and memory formation, by controlling mRNA translation efficiency via 3' untranslated regions (3'UTR). In the present study, we show that CPEB1 is significantly downregulated in human Glioblastoma Multiforme (GBM) tissues and that the restoration of its expression impairs glioma cell lines growth. We demonstrate that CPEB1 promotes the expression of the cell cycle inhibitor p27(Kip1) by specifically targeting its 3'UTR, and competes with miR-221/222 binding at an overlapping site in the 3'UTR, thus impairing miR-221/222 inhibitory activity. Upon binding to p27(Kip1) 3'UTR, CPEB1 promotes elongation of poly-A tail and the subsequent translation of p27(Kip1) mRNA. This leads to higher levels of p27(Kip1) in the cell, in turn significantly inhibiting cell proliferation, and confers to CPEB1 a potential value as a tumor suppressor in Glioblastoma.
authors.affiliation: Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galardi
authors.affiliation: Institute for Integrative Biology of the Cell, IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Petretich
authors.affiliation: Institute for Integrative Biology of the Cell, IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pinna
authors.affiliation: 3Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: D'Amico
authors.affiliation: 3Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Loreni
authors.affiliation: Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Michienzi
authors.affiliation: Institute for Integrative Biology of the Cell, IBITECS, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Irina
authors.initials: I
authors.lastname: Groisman
authors.affiliation: Department of Biomedicine and Prevention, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Silvia Anna
authors.initials: SA
authors.lastname: Ciafrè
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009457:Neuroglia / Q000502:physiology; D014176:Protein Biosynthesis; D014157:Transcription Factors / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
chemical_list: C436291:CDKN1B protein, human; C490386:CPEB1 protein, human; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27