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Molecular and Cellular Biology, July 2001, p. 4837-4846, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4837-4846.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cell-Specific Association and Shuttling of Ikappa Balpha Provides a Mechanism for Nuclear NF-kappa B in B Lymphocytes

Winnie F. Tam, Weihong Wang,dagger and Ranjan Sen*

Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02454

Received 20 December 2000/Returned for modification 18 February 2001/Accepted 9 April 2001

Mature B lymphocytes are unique in containing nuclear Rel proteins prior to cell stimulation. This activity consists largely of p50-c-Rel heterodimers, and its importance for B-cell function is exemplified by reduced B-cell viability in several genetically altered mouse strains. Here we suggest a mechanism for the cell specificity and the subunit composition of constitutive B-cell NF-kappa B based on the observed properties of Rel homo- and heterodimers and Ikappa Balpha . We show that c-Rel lacks a nuclear export sequence, making the removal of c-Rel-containing complexes from the nucleus less efficient than removal of p65-containing complexes. Second, the nuclear import potential of p65 and c-Rel homodimers but not p50-associated heterodimers was attenuated when they were complexed to Ikappa Balpha , leading to a greater propensity of heterodimers to be nuclear. We propose that subunit composition of B-cell NF-kappa B reflects the inefficient retrieval of p50-c-Rel heterodimers from the nucleus. Cell specificity may be a consequence of c-Rel-Ikappa Balpha complexes being present only in mature B cells, which leads to nuclear c-Rel due to Ikappa Balpha turnover and shuttling of the complex.


* Corresponding author. Mailing address: Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA 02454. Phone: (781) 736-2454. Fax: (781) 736-2405. E-mail: sen{at}brandeis.edu.

dagger Present address: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129.


Molecular and Cellular Biology, July 2001, p. 4837-4846, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4837-4846.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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