The eIF4E-binding proteins 1 and 2 are negative regulators of cell growth

Oncogene. 1996 Dec 5;13(11):2415-20.


Initiation in eukaryotes is the rate limiting step of translation. The binding of the mRNA to the 40S ribosomal subunit, which is mediated by the mRNA cap structure, is a key target for control of protein synthesis. The cap binding protein, eIF4E, is the most limiting of all initiation factors and its overexpression in NIH3T3 cells causes malignant transformation. 4E-binding protein 1 (BP1) and 4E-BP2 are small proteins that bind to eIF4E and inhibit translation. Here, 4E-BPs were expressed in cells transformed by eIF4E or by v-src to determine the effect of 4E-BPs on cell growth and tumorigenicity. We show that 4E-BPs cause a significant reversion of the transformed phenotype. Thus, we demonstrate that the eIF4E-binding proteins act as negative regulators of cell growth. We propose that 4E-BPs are members of a class of negative regulators of cell growth acting on the translation machinery of the cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / metabolism
  • 3T3 Cells / pathology
  • Animals
  • Cell Division / genetics*
  • Colony-Forming Units Assay
  • Cyclins / metabolism
  • Mice
  • Mice, Nude
  • Ornithine Decarboxylase / metabolism
  • Peptide Initiation Factors / metabolism*
  • Phenotype
  • Protein Biosynthesis*
  • RNA Cap-Binding Proteins
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism*


  • Cyclins
  • Peptide Initiation Factors
  • RNA Cap-Binding Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ornithine Decarboxylase