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Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap.

A Lazaris-Karatzas·K S Montine·N Sonenberg
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Abstract

Eukaryotic cellular mRNAs have a 5' cap structure (m7 GpppX) that facilitates binding to ribosomes and is required for efficient translation. A specific initiation factor, eIF-4F, mediates the function of the cap and consists of three subunits, one of which, eIF-4E, binds the cap. This subunit is present in limiting amounts in the cell, and is thought to be regulated by phosphorylation: decreased phosphorylation of eIF-4E following various treatments correlates with a decrease in cellular translation rate. These observations suggest that eIF-4E lies on the mitogenic signal transduction pathway, and we reasoned that overexpression of eIF-4E might profoundly affect cellular growth properties. We report here that overexpression of eIF-4E in NIH 3T3 and Rat 2 fibroblasts causes their tumorigenic transformation as determined by three criteria: formation of transformed foci on a monolayer of cells; anchorage-independent growth; and tumour formation in nude mice.

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AnimalsBlotting, NorthernCell DivisionCell LineCell Transformation, NeoplasticCloning, MolecularEukaryotic Initiation Factor-4FGene ExpressionMiceMice, NudeNeoplasms, ExperimentalPeptide Initiation FactorsProtein BiosynthesisRNA CapsRNA, MessengerRatsSignal TransductionJournal ArticleResearch Support, Non-U.S. Gov't

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A Lazaris-Karatzas, K S Montine, N Sonenberg. 1990-06-07. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap.. https://doi.org/10.1038/345544a0

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