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Mol Cell Biol, May 1998, p. 2524-2534, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Nuclear Localization of Ikappa Balpha Is Mediated by the Second Ankyrin Repeat: the Ikappa Balpha Ankyrin Repeats Define a Novel Class of cis-Acting Nuclear Import Sequences

Shrikesh Sachdev,1 Alexander Hoffmann,2 and Mark Hannink1,*

Biochemistry Department, University of Missouri---Columbia, Columbia, Missouri 65212,1 and Division of Biology, California Institute of Technology, Pasadena, California 911252

Received 10 October 1997/Returned for modification 11 November 1997/Accepted 20 February 1998

The ability of the Ikappa Balpha protein to sequester dimeric NF-kappa B/Rel proteins in the cytoplasm provides an effective mechanism for regulating the potent transcriptional activation properties of NF-kappa B/Rel family members. Ikappa Balpha can also act in the nucleus as a postinduction repressor of NF-kappa B/Rel proteins. The mechanism by which Ikappa Balpha enters the nucleus is not known, as Ikappa Balpha lacks a discernible classical nuclear localization sequence (NLS). We now report that nuclear localization of Ikappa Balpha is mediated by a novel nuclear import sequence within the second ankyrin repeat. Deletion of the second ankyrin repeat or alanine substitution of hydrophobic residues within the second ankyrin repeat disrupts nuclear localization of Ikappa Balpha . Furthermore, a region encompassing the second ankyrin repeat of Ikappa Balpha is able to function as a discrete nuclear import sequence. The presence of a discrete nuclear import sequence in Ikappa Balpha suggests that cytoplasmic sequestration of the NF-kappa B/Rel-Ikappa Balpha complex is a consequence of the mutual masking of the NLS within NF-kappa B/Rel proteins and the import sequence within Ikappa Balpha . Nuclear import may be a conserved property of ankyrin repeat domains (ARDs), as the ARDs from two other ARD-containing proteins, 53BP2 and GABPbeta , are also able to function as nuclear import sequences. We propose that the Ikappa Balpha ankyrin repeats define a novel class of cis-acting nuclear import sequences.

* Corresponding author. Mailing address: Biochemistry Department, University of Missouri---Columbia, M121 Medical Sciences Building, Columbia, MO 65212. Phone: (573) 882-7971. Fax: (573) 884-4597. E-mail: bcmarkh{at}muccmail.missouri.edu.

Mol Cell Biol, May 1998, p. 2524-2534, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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