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

Nature volume 345, pages 544–547 (1990)Cite this article

Abstract

EUKARYOTIC cellular mRNAs have a 5' cap structure (m7 GpppX) that facilitates binding to ribosomes and is required for efficient translation1–3. A specific initiation factor, eIF-4F, mediates the function of the cap4–6 and consists of three subunits7–10, one of which, eIF-4E, binds the cap. This subunit is present in limiting amounts in the cell11–13, and is thought to be regulated by phosphorylation12–16: 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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Authors and Affiliations

  1. Department of Biochemistry, McGill University, Montreal, Quebec, H3G 1Y6, Canada

    Anthoula Lazaris-Karatzas, Kathleen S. Montine & Nahum Sonenberg

  2. McGill Cancer Centre, McGill University, Montreal, Quebec, H3G 1Y6, Canada

    Nahum Sonenberg

Authors
  1. Anthoula Lazaris-Karatzas
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  2. Kathleen S. Montine
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  3. Nahum Sonenberg
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Lazaris-Karatzas, A., Montine, K. & Sonenberg, N. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap. Nature 345, 544–547 (1990). https://doi.org/10.1038/345544a0

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