Eukaryotic Cell
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Eukaryotic Cell, April 2003, p. 209-221, Vol. 2, No. 2
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.2.209-221.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Nuclear Import of Zinc Binuclear Cluster Proteins Proceeds through Multiple, Overlapping Transport Pathways

Igor Nikolaev, Marie-Françoise Cochet,{dagger} and Béatrice Felenbok*

Institut de Génétique et Microbiologie, Université Paris-Sud, UMR 8621 CNRS, Centre d'Orsay, 91405 Orsay Cedex, France

Received 27 August 2002/ Accepted 6 January 2003

In Aspergillus nidulans, the high transcriptional level of the ethanol utilization pathway genes (alc) is regulated by the specific activator AlcR. Here we have analyzed the mechanism of the nuclear import of AlcR, as well as that of other proteins belonging to the Zn2Cys6 binuclear cluster family. The nuclear localization signal of AlcR maps within the N-terminal 75 amino acid residues and overlaps with its DNA-binding domain. It consists of five clusters rich in basic residues. Four of them are necessary and sufficient for nuclear targeting. The first two basic regions are crucial for both nuclear localization and recognition of AlcR-specific DNA targets. This nuclear localization signal (NLS) motif is recognized by the nuclear transport machinery of Saccharomyces cerevisiae and requires both Ran/Gsp1p activity and specific transport receptors. AlcR can be imported into nuclei via multiple transport pathways mediated by a distinct set of karyopherins composed of Kap104p, Sxm1p, and Nmd5p transport receptors. The two former karyopherins interact with the NLS of AlcR directly. Other Zn binuclear cluster proteins from S. cerevisiae, such as Gal4p and Pdr3p, also appear to be transported to the nuclei in a nonclassical, importin-{alpha}-independent manner and can share common importin ß receptors.

* Corresponding author. Mailing address: Institut de Génétique et Microbiologie, BÂtiment 409, Centre d'Orsay, 91405 Orsay Cedex, France. Phone: 33169156328. Fax: 33169157808. E-mail: felenbok{at}igmors.u-psud.fr.

{dagger} Present address: ENSA Département Agro-Alimentaire, Laboratoire de Microbiologie, 35042 Rennes Cedex, France.

Eukaryotic Cell, April 2003, p. 209-221, Vol. 2, No. 2
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.2.209-221.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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