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* Zentrum für Molekulare Biologie der Universität Heidelberg, 69120 Heidelberg, Germany; The importin-
Max-Delbrück-Zentrum für
Molekulare Medizin, 13122 Berlin-Buch, Germany; § Abteilung Molekulare Biologie der Mitose, Deutsches
Krebsforschungszentrum, 69120 Heidelberg, Germany;
European Molecular Biology Laboratory, 69117 Heidelberg, Germany; ¶ Institut für Biochemie, Humboldt Universität Berlin, 10115 Berlin, Germany; and ** University of Geneva, Department of
Molecular Biology, CH-1211 Geneva 4, Switzerland
/
complex and the GTPase
Ran mediate nuclear import of proteins with a classical
nuclear localization signal. Although Ran has been implicated also in a variety of other processes, such as cell
cycle progression, a direct function of Ran has so far
only been demonstrated for importin-mediated nuclear
import. We have now identified an entire class of ~20
potential Ran targets that share a sequence motif related to the Ran-binding site of importin-
. We have
confirmed specific RanGTP binding for some of them,
namely for two novel factors, RanBP7 and RanBP8, for CAS, Pse1p, and Msn5p, and for the cell cycle regulator
Cse1p from Saccharomyces cerevisiae. We have studied
RanBP7 in more detail. Similar to importin-
, it prevents the activation of Ran's GTPase by RanGAP1 and
inhibits nucleotide exchange on RanGTP. RanBP7
binds directly to nuclear pore complexes where it competes for binding sites with importin-
, transportin, and
apparently also with the mediators of mRNA and U
snRNA export. Furthermore, we provide evidence for
a Ran-dependent transport cycle of RanBP7 and demonstrate that RanBP7 can cross the nuclear envelope
rapidly and in both directions. On the basis of these results, we propose that RanBP7 might represent a nuclear transport factor that carries an as yet unknown
cargo, which could apply as well for this entire class of
related RanGTP-binding proteins.
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