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 structure m(7)GpppN (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 alphabeta 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 alphabeta pathway by a piggy-back mechanism.
Dostie
J
J
Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir-William-Osler, Montréal, Québec H3G 1Y6, Canada.
Ferraiuolo
M
M
Pause
A
A
Adam
S A
SA
Sonenberg
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002451:Cell Compartmentation; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E; D015723:Gene Library; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D010448:Peptide Initiation Factors / Q000378:metabolism*; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; C411571:EIF4ENIF1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D010448:Peptide Initiation Factors