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Molecular and Cellular Biology, September 1999, p. 6276-6285, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

RanGTP-Regulated Interactions of CRM1 with Nucleoporins and a Shuttling DEAD-Box Helicase

Peter Askjaer,1,2 Angela Bachi,3 Matthias Wilm,3 F. Ralf Bischoff,4 Daniel L. Weeks,5 Vera Ogniewski,5 Mutsuhito Ohno,1 Christof Niehrs,6 Jørgen Kjems,2 Iain W. Mattaj,1,* and Maarten Fornerod1

Departments of Gene Expression1 and Biochemical Instrumentation,3 European Molecular Biology Laboratory, and Biology of Mitosis4 and Molecular Embryology,6 Deutsches Krebsforschungszentrum, Heidelberg, Germany; Department of Molecular and Structural Biology, University of Aarhus, Aarhus, Denmark2; and Department of Biochemistry, University of Iowa, Iowa City, Iowa5

Received 22 March 1999/Returned for modification 5 May 1999/Accepted 21 June 1999

CRM1 is an export receptor mediating rapid nuclear exit of proteins and RNAs to the cytoplasm. CRM1 export cargoes include proteins with a leucine-rich nuclear export signal (NES) that bind directly to CRM1 in a trimeric complex with RanGTP. Using a quantitative CRM1-NES cargo binding assay, significant differences in affinity for CRM1 among natural NESs are demonstrated, suggesting that the steady-state nucleocytoplasmic distribution of shuttling proteins could be determined by the relative strengths of their NESs. We also show that a trimeric CRM1-NES-RanGTP complex is disassembled by RanBP1 in the presence of RanGAP, even though RanBP1 itself contains a leucine-rich NES. Selection of CRM1-binding proteins from Xenopus egg extract leads to the identification of an NES-containing DEAD-box helicase, An3, that continuously shuttles between the nucleus and the cytoplasm. In addition, we identify the Xenopus homologue of the nucleoporin CAN/Nup214 as a RanGTP- and NES cargo-specific binding site for CRM1, suggesting that this nucleoporin plays a role in export complex disassembly and/or CRM1 recycling.

* Corresponding author. Mailing address: EMBL---Gene Expression, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Phone: 49-6221-387317. Fax: 49-6221-387518. E-mail: mattaj{at}embl-heidelberg.de.

Molecular and Cellular Biology, September 1999, p. 6276-6285, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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