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Molecular and Cellular Biology, October 1999, p. 7088-7095, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Regulation of RelA Subcellular Localization by a Putative Nuclear Export Signal and p50

Edward W. Harhaj and Shao-Cong Sun*

Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, Hershey, Pennsylvania 17033

Received 19 February 1999/Returned for modification 1 April 1999/Accepted 12 July 1999

Nuclear factor kappa B (NF-kappa B) represents a family of dimeric DNA binding proteins, the pleotropic form of which is a heterodimer composed of RelA and p50 subunits. The biological activity of NF-kappa B is controlled through its subcellular localization. Inactive NF-kappa B is sequestered in the cytoplasm by physical interaction with an inhibitor, Ikappa Balpha . Signal-mediated Ikappa Balpha degradation triggers the release and subsequent nuclear translocation of NF-kappa B. It remains unknown whether the NF-kappa B shuttling between the cytoplasm and nucleus is subjected to additional steps of regulation. In this study, we demonstrated that the RelA subunit of NF-kappa B exhibits strong cytoplasmic localization activity even in the absence of Ikappa Balpha inhibition. The cytoplasmic distribution of RelA is largely mediated by a leucine-rich sequence homologous to the recently characterized nuclear export signal (NES). This putative NES is both required and sufficient to mediate cytoplasmic localization of RelA as well as that of heterologous proteins. Furthermore, the cytoplasmic distribution of RelA is sensitive to a nuclear export inhibitor, leptomycin B, suggesting that RelA undergoes continuous nuclear export. Interestingly, expression of p50 prevents the cytoplasmic expression of RelA, leading to the nuclear accumulation of both RelA and p50. Together, these results suggest that the nuclear and cytoplasmic shuttling of RelA is regulated by both an intrinsic NES-like sequence and the p50 subunit of NF-kappa B.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-4164. Fax: (717) 531-6522. E-mail: sxs70{at}psu.edu.

Molecular and Cellular Biology, October 1999, p. 7088-7095, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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