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

The eukaryotic translation initiation factor 4E (eIF4E) plays an important role in the control of cell growth. eIF4E binds to the mRNA 5' cap structur e m(7)GpppN (where N is any nucleotide), and promotes ribosome binding to t he mRNA in the cytoplasm. However, a fraction of eIF4E localizes to the nuc leus. Here we describe the cloning and functional characterization of a new eIF4E-binding protein, referred to as 4E-T (eIF4E-Transporter) We demonstr ate that 4E-T is a nucleocytoplasmic shuttling protein that contains an eIF 4E-binding site, one bipartite nuclear localization signal and two leucine- rich nuclear export signals. eIF4E forms a complex with the importin alpha beta 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 a ccumulation of HA-eIF4E in cells treated with leptomycin B. Taken together, these results demonstrate that the novel nucleocytoplasmic shuttling prote in 4E-T mediates the nuclear import of eIF4E via the importin alpha beta pa thway by a piggy-back mechanism.