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Molecular and Cellular Biology, March 2000, p. 1571-1582, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Nuclear Import of Ikappa Balpha Is Accomplished by a Ran-Independent Transport Pathway

Shrikesh Sachdev,dagger Sriparna Bagchi, Donna D. Zhang, Angela C. Mings, and Mark Hannink*

Biochemistry Department, University of Missouri---Columbia, Columbia, Missouri 65212

Received 9 June 1999/Returned for modification 27 July 1999/Accepted 10 December 1999

The inhibitor of kappa B alpha (Ikappa Balpha ) protein is able to shuttle between the cytoplasm and the nucleus. We have utilized a combination of in vivo and in vitro approaches to provide mechanistic insight into nucleocytoplasmic shuttling by Ikappa Balpha . Ikappa Balpha contains multiple functional domains that contribute to shuttling of Ikappa Balpha between the cytoplasm and the nucleus. Nuclear import of Ikappa Balpha is mediated by the central ankyrin repeat domain. Similar to previously described nuclear import pathways, nuclear import of Ikappa Balpha is temperature and ATP dependent and is blocked by a dominant-negative mutant of importin beta . However, in contrast to classical nuclear import pathways, nuclear import of Ikappa Balpha is independent of soluble cytosolic factors and is not blocked by the dominant-negative RanQ69L protein. Nuclear export of Ikappa Balpha is mediated by an N-terminal nuclear export sequence. Nuclear export of Ikappa Balpha requires the CRM1 nuclear export receptor and is blocked by the dominant-negative RanQ69L protein. Our results are consistent with a model in which nuclear import of Ikappa Balpha is mediated through direct interactions with components of the nuclear pore complex, while nuclear export of Ikappa Balpha is mediated via a CRM1-dependent pathway.

* Corresponding author. Mailing address: Biochemistry Department, University of Missouri---Columbia, Columbia, MO 65212. Phone: (573) 882-7971. Fax: (573) 882-1378. E-mail: HanninkM{at}missouri.edu.

dagger Present address: Institute for Biochemistry and Gene Center, Ludwig-Maxmillian University, Munich, Germany.

Molecular and Cellular Biology, March 2000, p. 1571-1582, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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