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Mol Cell Biol, March 1998, p. 1213-1224, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Distinct Domains of Ikappa Balpha Regulate c-Rel in the Cytoplasm and in the Nucleus

Ignacio Luque1 and Céline Gélinas1,2,3,*

Center for Advanced Biotechnology and Medicine,1 Department of Biochemistry, Robert Wood Johnson Medical School,2 and Cancer Institute of New Jersey,3 University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-5638

Received 20 October 1997/Accepted 5 December 1997

Ikappa Balpha is a critical regulator of Rel/NF-kappa B-mediated gene activation. It controls the induction of NF-kappa B factors by retaining them in the cytoplasm and also functions in the nucleus to terminate the induction process. In this study, we show that Ikappa Balpha regulates the transcriptional activity of c-Rel in the nuclear compartment. We also demonstrate that discrete functional domains of Ikappa Balpha are responsible for the cytoplasmic and nuclear regulation of c-Rel. We show that the determinants for the cytoplasmic regulation of c-Rel reside in the N-terminal and central ankyrin regions of Ikappa Balpha and that the N-terminal domain of Ikappa Balpha is required to mask the c-Rel nuclear localization signal. Importantly, Ikappa Balpha sequences necessary to regulate c-Rel in the nucleus map to its central ankyrin domain and to a few negatively charged amino acids that immediately follow in the C-terminal Ikappa Balpha PEST domain. The mapping of the Ikappa Balpha determinants that control the cytoplasmic and nuclear activities of c-Rel to specific regions of the molecule suggests that Ikappa Balpha inhibitors could be designed to antagonize Rel/NF-kappa B activity in different subcellular compartments or at defined stages of activation.

* Corresponding author. Mailing address: CABM, 679 Hoes Ln., Piscataway, NJ 08854-5638. Phone: (732) 235-5035. Fax: (732) 235-5289. E-mail: gelinas{at}mbcl.rutgers.edu.




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