A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5' cap-binding protein, eIF4E

Josée Dostie, Maria Ferraiuolo, Arnim Pause, Stephen A. Adam, Nahum Sonenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

The eukaryotic translation initiation factor 4E (eIF4E) plays an important role in the control of cell growth. eIF4E binds to the mRNA 5' cap structure m7GpppN (where N is any nucleotide), and promotes ribosome binding to the mRNA in the cytoplasm. However, a fraction of eIF4E localizes to the nucleus. Here we describe the cloning and functional characterization of a new eIF4E-binding protein, referred to as 4E-T (eIF4E-Transporter). We demonstrate that 4E-T is a nucleocytoplasmic shuttling protein that contains an eIF4E-binding site, one bipartite nuclear localization signal and two leucine-rich nuclear export signals. eIF4E forms a complex with the importin αβ heterodimer only in the presence of 4E-T. Overexpression of wild-type 4E-T, but not of a mutant defective for eIF4E binding, causes the nuclear accumulation of HA-eIF4E in cells treated with leptomycin B. Taken together, these results demonstrate that the novel nucleocytoplasmic shuttling protein 4E-T mediates the nuclear import of eIF4E via the importin αβ pathway by a piggy-back mechanism.

Original languageEnglish (US)
Pages (from-to)3142-3156
Number of pages15
JournalEMBO Journal
Volume19
Issue number12
DOIs
StatePublished - Jun 15 2000

Keywords

  • Cap-binding protein
  • Initiation factor
  • Shuttling protein
  • Transport
  • eIF4E localization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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