Translational regulation of the mammalian growth-related protein P23: involvement of eIF-4E.

Abstract

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.

• Authors: U A Bommer, A Lazaris-Karatzas, A De Benedetti, P Nürnberg, R Benndorf, H Bielka, N Sonenberg
• Journal: Cellular & molecular biology research (Cell Mol Biol Res) Vol. 40 Issue 7-8 Pg. 633-41 ( 1994) ISSN: 0968-8773 [Print] United States
• PMID: 7787881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Biomarkers, Tumor
• Eukaryotic Initiation Factor-4E
• Growth Substances
• Insulin
• Neoplasm Proteins
• Peptide Initiation Factors
• Peptides
• Recombinant Proteins
• Sulfur Radioisotopes
• Tumor Protein, Translationally-Controlled 1
• Epidermal Growth Factor
• Bucladesine
• Methionine
• Tetradecanoylphorbol Acetate

Topics

• 3T3 Cells
• Amino Acid Sequence
• Animals
• Antibodies
• Biomarkers, Tumor
• Blotting, Western
• Bucladesine (pharmacology)
• Carcinoma, Ehrlich Tumor (metabolism)
• Cell Division
• Epidermal Growth Factor (pharmacology)
• Eukaryotic Initiation Factor-4E
• Fibroblasts (cytology, metabolism)
• Gene Expression Regulation (drug effects)
• Growth Substances (analysis, biosynthesis)
• HeLa Cells
• Hot Temperature
• Humans
• Insulin (pharmacology)
• Methionine (metabolism)
• Mice
• Molecular Sequence Data
• Neoplasm Proteins (analysis, biosynthesis)
• Peptide Initiation Factors (biosynthesis, metabolism)
• Peptides (chemical synthesis, immunology)
• Phosphorylation
• Protein Biosynthesis (drug effects)
• Rabbits (immunology)
• Recombinant Proteins (biosynthesis, metabolism)
• Sulfur Radioisotopes
• Tetradecanoylphorbol Acetate (pharmacology)
• Transfection
• Tumor Cells, Cultured
• Tumor Protein, Translationally-Controlled 1