Malignant Transformation by a Eukaryotic Initiation Factor Subunit That Binds to mRNA 5' Cap

Nature. 1990 Jun 7;345(6275):544-7. doi: 10.1038/345544a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Division
  • Cell Line
  • Cell Transformation, Neoplastic / genetics*
  • Cloning, Molecular
  • Eukaryotic Initiation Factor-4F
  • Gene Expression
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / genetics
  • Peptide Initiation Factors / physiology*
  • Protein Biosynthesis
  • RNA Caps / metabolism*
  • RNA, Messenger / genetics
  • Rats
  • Signal Transduction

Substances

  • Eukaryotic Initiation Factor-4F
  • Peptide Initiation Factors
  • RNA Caps
  • RNA, Messenger