title: GAP-43 slows down cell cycle progression via sequences in its 3'UTR.
abstract: Growth-associated protein 43 (GAP-43) is a neuronal phosphoprotein associated with initial axonal outgrowth and synaptic remodeling and recent work also suggests its involvement in cell cycle control. The complex expression of GAP-43 features transcriptional and posttranscriptional components. However, in some conditions, GAP-43 gene expression is controlled primarily by the interaction of stabilizing or destabilizing RNA-binding proteins (RBPs) with adenine and uridine (AU)-rich instability elements (AREs) in its 3'UTR. Like GAP-43, many proteins involved in cell proliferation are encoded by ARE-containing mRNAs, some of which codify cell-cycle-regulating proteins including cyclin D1. Considering that GAP-43 and cyclin D1 mRNA stabilization may depend on similar RBPs, this study evaluated the participation of GAP-43 in cell cycle control and its underlying mechanisms, particularly the possible role of its 3'UTR, using GAP-43-transfected NIH-3T3 fibroblasts. Our results show an arrest in cell cycle progression in the G0/G1 phase. This arrest may be mediated by the competition of GAP-43 3'UTR with cyclin D1 3'UTR for the binding of Hu proteins such as HuR, which may lead to a decrease in cyclin D1 expression. These results might lead to therapeutic applications involving the use of sequences in the B region of GAP-43 3'UTR to slow down cell cycle progression.
authors.affiliation: Department of Biological Chemistry, IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina.
authors.forename: Karina
authors.initials: K
authors.lastname: De Moliner
authors.affiliation: Department of Biological Chemistry, IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina.
authors.forename: Manuel Luis
authors.initials: ML
authors.lastname: Wolfson
authors.affiliation: Department of Neurosciences and Psychiatry, University of New Mexico School of Medicine, Albuquerque, NM, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Perrone-Bizzozero
authors.affiliation: Department of Biological Chemistry, IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina. Electronic address: amadamo@qb.ffyb.uba.ar.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Adamo
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004789:Enzyme Activation; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D041681:NIH 3T3 Cells; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D016213:Cyclins; D019922:GAP-43 Protein; D016601:RNA-Binding Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: 3′UTR; Cell cycle control; GAP-43; RNA-binding protein