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Molecular and Cellular Biology, April 2000, p. 2687-2695, Vol. 20, No. 8
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Rel/NF-kappa B Family Directly Activates Expression of the Apoptosis Inhibitor Bcl-xL

Cailin Chen,1,dagger Leonard C. Edelstein,1,2 and Céline Gélinas1,3,*

Center for Advanced Biotechnology and Medicine,1 Graduate Programs in Biochemistry and Molecular Biology and in Biotechnology,2 and Department of Biochemistry,3 Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-5638

Received 6 August 1999/Returned for modification 23 September 1999/Accepted 31 January 2000

The transcription factors of the Rel/NF-kappa B family are key regulators of immune and inflammatory responses and contribute to lymphocyte proliferation, survival, and oncogenesis. The absolute correlation between the antiapoptotic and oncogenic activities of the Rel/NF-kappa B oncoprotein v-Rel emphasizes the importance of characterizing the death antagonists under NF-kappa B control. Our recent finding that the prosurvival Bcl-2 homolog Bfl-1 (also called A1) is a direct transcriptional target of NF-kappa B raised the issue of whether NF-kappa B is a specific or global regulator of death antagonists in the Bcl-2 family. Here, we demonstrate that NF-kappa B differentially regulates the expression of particular Bcl-2-related death inhibitors and that it directly activates the expression of Bcl-xL. While Bcl-xL was significantly upregulated by c-Rel and RelA, Bcl-2 was not. Importantly, stimuli that activate endogenous NF-kappa B factors also upregulated bcl-x gene expression and this effect was antagonized by an inhibitor of NF-kappa B activity. The expression of bcl-x suppressed apoptosis in the presence or absence of NF-kappa B activity. Functional analysis of the bcl-x promoter demonstrated that it is directly controlled by c-Rel. These results establish that NF-kappa B directly regulates the expression of distinct prosurvival factors in the Bcl-2 family, such as Bcl-xL and Bfl-1/A1. These findings raise the possibility that some of these factors may contribute to oncogenesis associated with aberrant Rel/NF-kappa B activity.

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

dagger Present address: The R. W. Johnson Pharmaceutical Research Institute, Johnson & Johnson Co., Springhouse, PA 19477.

Molecular and Cellular Biology, April 2000, p. 2687-2695, Vol. 20, No. 8
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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