Exportin 4: a mediator of a novel nuclear export pathway in higher eukaryotes.
Transport receptors of the importin beta superfamily account for many of the nuclear import and export events in eukaryotic cells. They mediate translocation through nuclear pore complexes, shuttle between nucleus and cytoplasm and co-operate with the RanGTPase system to regulate their interactions with cargo molecules in a compartment-specific manner. We used affinity chromatography on immobilized RanGTP to isolate further candidate nuclear transport receptors and thereby identified exportin 4 as the most distant member of the importin beta family so far. Exportin 4 appears to be conserved amongst higher eukaryotes, but lacks obvious orthologues in yeast. It mediates nuclear export of eIF-5A (eukaryotic translation initiation factor 5A) and possibly that of other cargoes. The export signal in eIF-5A appears to be complex and to involve the hypusine modification that is unique to eIF-5A. We discuss possible cellular roles for nuclear export of eIF-5A.
Lipowsky
G
G
ZMBH, 69120 Heidelberg, Germany.
Bischoff
F R
FR
Schwarzmaier
P
P
Kraft
R
R
Kostka
S
S
Hartmann
E
E
Kutay
U
U
Görlich
D
D
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D013997:Time Factors; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
D002352:Carrier Proteins; D018076:DNA, Complementary; D020558:GTP Phosphohydrolases; D028884:Karyopherins; D008239:Lysine; D009687:Nuclear Proteins; D010448:Peptide Initiation Factors; D012313:RNA; D016601:RNA-Binding Proteins; D020931:ran GTP-Binding Protein; D000097574:Eukaryotic Translation Initiation Factor 5A; C414440:Xpo4 protein, human; C485892:Xpo4 protein, mouse; C100028:hypusine