Ras mediates translation initiation factor 4E-induced malignant transformation
| Autor: | Nahum Sonenberg, R. M. Frederickson, Jaramillo M, Hsiang-Fu Kung, M. R. Smith, A. Lazaris-Karatzas, Ya-Lun Liu |
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| Rok vydání: | 1992 |
| Předmět: |
GTPase-activating protein
Carcinogenicity Tests Blotting Western macromolecular substances Biology environment and public health Proto-Oncogene Proteins p21(ras) Mice Eukaryotic translation Peptide Initiation Factors Eukaryotic initiation factor Genetics Animals Initiation factor heterocyclic compounds GTPase-Activating Proteins Proteins 3T3 Cells EIF4A1 Blotting Northern musculoskeletal system Molecular biology Eukaryotic translation initiation factor 4 gamma Cell biology Cell Transformation Neoplastic Eukaryotic Initiation Factor-4E Ras Signaling Pathway ras GTPase-Activating Proteins Protein Biosynthesis Mutation health occupations Signal transduction Signal Transduction Developmental Biology |
| Zdroj: | Genes & Development. 6:1631-1642 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.6.9.1631 |
| Popis: | Translation initiation factor eIF-4E binds to the eukaryotic mRNA 5' cap structure (m7 GpppN, where N is any nucleotide). eIF-4E is a limiting factor in translation and plays a key role in regulation of translation. We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells. To understand the mechanisms by which eIF-4E exerts its mitogenic property, we examined the involvement of the Ras signaling pathway in this activity. Here, we report that Ras is activated in eIF-4E-overexpressing cells, as the proportion of GTP-bound Ras is increased. Overexpression of the negative effector of cellular Ras, GTPase activating protein, causes reversion of the transformed phenotype. Furthermore, we show that neutralizing antibodies to Ras, or a dominant-negative mutant of Ras, inhibit the mitogenic activity of eIF-4E. We conclude that eIF-4E exerts its mitogenic and oncogenic activities by the activation of Ras. |
| Databáze: | OpenAIRE |
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