title: The eIF4E-binding proteins 1 and 2 are negative regulators of cell growth.
abstract: Initiation in eukaryotes is the rate limiting step of translation. The binding of the mRNA to the 40S ribosomal subunit, which is mediated by the mRNA cap structure, is a key target for control of protein synthesis. The cap binding protein, eIF4E, is the most limiting of all initiation factors and its overexpression in NIH3T3 cells causes malignant transformation. 4E-binding protein 1 (BP1) and 4E-BP2 are small proteins that bind to eIF4E and inhibit translation. Here, 4E-BPs were expressed in cells transformed by eIF4E or by v-src to determine the effect of 4E-BPs on cell growth and tumorigenicity. We show that 4E-BPs cause a significant reversion of the transformed phenotype. Thus, we demonstrate that the eIF4E-binding proteins act as negative regulators of cell growth. We propose that 4E-BPs are members of a class of negative regulators of cell growth acting on the translation machinery of the cell.
authors.affiliation: Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Rousseau
authors.forename: A C
authors.initials: AC
authors.lastname: Gingras
authors.forename: A
authors.initials: A
authors.lastname: Pause
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D016475:3T3 Cells / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000235:genetics*; D003114:Colony-Forming Units Assay; D016213:Cyclins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010641:Phenotype; D014176:Protein Biosynthesis; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D016213:Cyclins; D010448:Peptide Initiation Factors; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D009955:Ornithine Decarboxylase