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

A Lazaris-Karatzas, KS Montine, N Sonenberg - Nature, 1990 - nature.com
Nature, 1990nature.com
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 …
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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