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© The Rockefeller University Press, 0021-9525/1997//65 $5.00
The Journal of Cell Biology, Volume 138, Number 1, , 1997 65-80

Article

A Novel Class of RanGTP Binding Proteins



Dirk Görlich*, Marylena Dabrowski*,{ddagger}, F. Ralf Bischoff§, Ulrike Kutay*, Peer Bork{ddagger},||, Enno Hartmann{ddagger}, Siegfried Prehn, and Elisa Izaurralde**

* Zentrum für Molekulare Biologie der Universität Heidelberg, 69120 Heidelberg, Germany; {ddagger} 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

The importin-{alpha}/β 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-β. 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-β, 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-β, 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.

1. Abbreviations used in this paper: GAP, GTPase activating protein; IBB, importin β binding; NLS, nuclear localization signal; NPC, nuclear pore complex.

Please address all correspondence to Dirk Görlich, Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. Tel.: (49) 6221-546862; Fax: (49) 6221-545892; E-mail: dg{at}mail.zmbh.uni-heidelberg.de


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