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J. Biol. Chem., Vol. 278, Issue 17, 15397-15405, April 25, 2003
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From The small Ras-like GTPase Ran plays an
essential role in the transport of macromolecules in and out of the
nucleus and has been implicated in spindle (1, 2) and nuclear
envelope formation (3, 4) during mitosis in higher eukaryotes. We
identified Saccharomyces cerevisiae open reading
frame YGL164c encoding a novel RanGTP-binding protein, termed
Yrb30p. The protein competes with yeast RanBP1 (Yrb1p) for binding to
the GTP-bound form of yeast Ran (Gsp1p) and is, like Yrb1p, able to
form trimeric complexes with RanGTP and some of the karyopherins. In
contrast to Yrb1p, Yrb30p does not coactivate but inhibits
RanGAP1(Rna1p)-mediated GTP hydrolysis on Ran, like the karyopherins.
At steady state, Yrb30p localizes exclusively to the cytoplasm, but the
presence of a functional nuclear export signal and the localization of truncated forms of Yrb30p suggest that the protein shuttles between nucleus and cytoplasm and is exported via two alternative pathways, dependent on the nuclear export receptor Xpo1p/Crm1p and on RanGTP binding. Whereas overproduction of the full-length protein and complete
deletion of the open reading frame reveal no obvious phenotype,
overproduction of C-terminally truncated forms of the protein inhibits
yeast vegetative growth. Based on these results and the exclusive
conservation of the protein in the fungal kingdom, we hypothesize that
Yrb30p represents a novel modulator of the Ran GTPase switch related to
fungal lifestyle.
Identification and Characterization of a Novel RanGTP-binding
Protein in the Yeast Saccharomyces cerevisiae*
,
,
,
, and
Biochemie-Zentrum Heidelberg,
Ruprecht-Karls-Universität, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany, § Departement des Biotechnologies,
Institut Pasteur, 25,28 rue du Docteur Roux, 75724 Paris CEDEX 15, France, ¶ Hybrigenics SA, 3-5 impasse Reille, 75014 Paris,
France,
Deutsches Krebsforschungszentrum, Im Neuenheimer
Feld 280, 69120 Heidelberg, Germany, and ** Mikrobiologisches
Institut, Eidgenössische Technische Hochschule,
Schmelzbergstrasse 7, 8092 Zürich, Switzerland
*
This work was supported in part by Deutsche
Forschungsgemeinschaft Research Grant Ku 1235/1-1 (to M. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.

To whom correspondence should be addressed:
Mikrobiologisches Institut, Eidgenössische Technische Hochschule
(ETH), ETH-Zentrum LFV E23, Schmelzbergstr. 7, CH-8092 Zürich,
Switzerland. Tel.: 41-1-632-4925; Fax: 41-1-632-1148; E-mail:
markus.kuenzler@micro.biol.ethz.ch.
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