Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

RNA. 2008 Jul;14(7):1318-27. doi: 10.1261/rna.950608. Epub 2008 May 30.


Eukaryotic initiation factor (eIF) 4E, the mRNA 5'-cap-binding protein, mediates the association of eIF4F with the mRNA 5'-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (approximately 30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Carrier Proteins / analysis
  • Cell Cycle Proteins
  • Cell Line
  • Cell Nucleus / chemistry
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Eukaryotic Initiation Factor-4E / analysis
  • Eukaryotic Initiation Factor-4E / metabolism*
  • Eukaryotic Initiation Factors
  • Fibroblasts / chemistry
  • Fibroblasts / cytology
  • Mice
  • Phosphoproteins / analysis
  • Phosphorylation
  • RNA, Messenger / metabolism


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • Eif4ebp1 protein, mouse
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factors
  • Phosphoproteins
  • RNA, Messenger