Nuclear import of c-Jun is mediated by multiple transport receptors.
c-Jun and c-Fos are major components of the transcriptional complex AP-1. Here, we investigate the nuclear import pathway(s) of the transcription factor c-Jun. c-Jun bound specifically to the nuclear import receptors importin beta, transportin, importin 5, importin 7, importin 9, and importin 13. In digitonin-permeabilized cells, importin beta, transportin, importin 7, and importin 9 promoted efficient import of c-Jun into the nucleus. Importin alpha, by contrast, inhibited nuclear import of c-Jun in vitro. A single basic region preceding the leucine zipper of c-Jun functions as a nuclear localization signal (NLS) and was required for interaction with all tested import receptors. In vivo, nuclear import of a c-Jun reporter protein lacking the leucine zipper strictly depended on this NLS. In a leucine zipper-dependent manner, c-Jun with mutations in its NLS was still imported into the nucleus in a complex with endogenous leucine zipper proteins or, for example, with cotransfected c-Fos. Together, these results explain the highly efficient nuclear import of the transcription factor c-Jun.
Waldmann
Inga
I
Universität Göttingen, Zentrum für Biochemie und Molekulare Zellbiologie, Humboldtallee 23, 37073 Göttingen, Germany.
Wälde
Sarah
S
Kehlenbach
Ralph H
RH
D021581:Active Transport, Cell Nucleus; D001692:Biological Transport; D003001:Cloning, Molecular; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D016350:Leucine Zippers; D009154:Mutation; D019913:Nuclear Localization Signals; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*
D028884:Karyopherins; D019913:Nuclear Localization Signals; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun