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Nature. 1990 Jun 7;345(6275):544-7.

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

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  • 1Department of Biochemistry, McGill University, Montreal, Quebec, Canada.


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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