title: Translation initiation factors induce DNA synthesis and transform NIH 3T3 cells.
abstract: Several polypeptide factors that are essential for the initiation of protein synthesis bind to eukaryotic mRNAs and facilitate the formation of ribosome initiation complexes. Purified mRNA-binding translation initiation factors were microinjected into quiescent NIH 3T3 cells to study the possible growth-promoting role of these factors in living cells. We report that recombinant eIF-4E and rabbit reticulocyte eIF-4F induce a dose-dependent increase of DNA synthesis and morphologically transform NIH 3T3 cells. These results suggest that polypeptides involved in activating the rate-limiting step of protein synthesis (initiation complex formation) can be mitogenic and oncogenic when overexpressed in a cell by direct injection. Thus, eIF-4E and eIF-4F represent a class of proto-oncogenic proteins that is cytoplasmic, is involved in protein synthesis initiation, and is distinct from the proto-oncogenes that have been identified previously.
authors.affiliation: Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick Cancer Research Facility, MD 21701.
authors.forename: M R
authors.initials: MR
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Jaramillo
authors.forename: Y L
authors.initials: YL
authors.lastname: Liu
authors.forename: T E
authors.initials: TE
authors.lastname: Dever
authors.forename: W C
authors.initials: WC
authors.lastname: Merrick
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000096:biosynthesis*; D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D008934:Mitogens; D010448:Peptide Initiation Factors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D008934:Mitogens; D010448:Peptide Initiation Factors; D011994:Recombinant Proteins; D004247:DNA