Translational regulation of the mammalian growth-related protein P23: involvement of eIF-4E
| Autor: | Ulrich Bommer, Lazaris-Karatzas A, De Benedetti A, Nürnberg P, Benndorf R, Bielka H, Sonenberg N |
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| Rok vydání: | 1994 |
| Předmět: |
Hot Temperature
Blotting Western Molecular Sequence Data Sulfur Radioisotopes Transfection Antibodies Mice Methionine Peptide Initiation Factors Biomarkers Tumor Tumor Cells Cultured Animals Humans Insulin Amino Acid Sequence Phosphorylation Carcinoma Ehrlich Tumor Growth Substances Epidermal Growth Factor Tumor Protein Translationally-Controlled 1 3T3 Cells Fibroblasts Recombinant Proteins Neoplasm Proteins Eukaryotic Initiation Factor-4E Bucladesine Gene Expression Regulation Protein Biosynthesis Tetradecanoylphorbol Acetate Rabbits Peptides Cell Division HeLa Cells |
| Zdroj: | Scopus-Elsevier Europe PubMed Central |
| ISSN: | 0968-8773 |
| Popis: | Synthesis of the mammalian growth-related protein P23 is rapidly induced after serum stimulation of mouse fibroblasts and Ehrlich ascites tumour cells. This induction occurs at the translational level. Growth-induction leads also to an increase in phosphorylation of the rate-limiting initiation factor eIF-4E. Here, we present the following evidence indicating the involvement of eIF-4E in the regulation of P23 synthesis: 1) P23 synthesis is induced by the same mitogenic stimuli which lead to enhanced eIF-4E phosphorylation. 2) Upon heat shock treatment of Ehrlich ascites cells (which results in immediate dephosphorylation and concomitant inactivation of eIF-4E), P23 synthesis is rapidly shut off. 3) In control NIH 3T3 cells, P23 synthesis is readily induced by growth stimulation. This response is strongly diminished in cells overexpressing eIF-4E, and the basal level of P23 synthesis is elevated in these cells. Overexpression of a nonfunctional mutant of eIF-4E diminishes the basal level of P23 synthesis as well as the serum-response of the cells with respect to P23 induction. 4) Cells transformed by overexpression of the ras or src genes in which eIF-4E is highly phosphorylated do not show any inducibility of P23 synthesis. 5) HeLa cells expressing antisense RNA of eIF-4E, have reduced levels of eIF-4E/F and show reduced rates of growth and protein synthesis. In these cells the total amount of P23 protein is about 50% compared with control cells. The results suggest that P23 is one of the gene products, the synthesis of which is regulated by eIF-4E activity. |
| Databáze: | OpenAIRE |
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