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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

Sachdev, Shrikesh and Hoffmann, Alexander and Hannink, Mark (1998) 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. Molecular and Cellular Biology, 18 (5). pp. 2524-2534. ISSN 0270-7306.

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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.

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Sachdev, Shrikesh0000-0002-2432-7070
Additional Information:Copyright © 1998, American Society for Microbiology. Received 10 October 1997/Returned for modification 11 November 1997/Accepted 20 February 1998 We thank Andrew Chappell for technical assistance and Dirk Görlich, J. Alan Diehl, and members of the Hannink laboratory for stimulating conversations. We thank Fernando Arenzana-Seisdedos, Dean Ballard, David Baltimore, Henry R. Bose, Anthony Capobianco, Dan Donoghue, Gideon Dreyfuss, Mark Martin, Gary Nabel, and Louie Naumovski for providing various reagents. This work was supported by Public Health Service grant CA-55027 from the National Cancer Institute, by USDA NRICGP award 95-04073, by University of Missouri Research Board grant RB97-175, and by the University of Missouri Molecular Biology Program.
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Deposited On:02 Nov 2006
Last Modified:09 Mar 2020 13:19

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