The Rel/NF-κb family directly activates expression of the apoptosis inhibitor BCl-x(L)

Cailin Chen, Leonard C. Edelstein, Céline Gélinas

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698 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)2687-2695
Number of pages9
JournalMolecular and cellular biology
Issue number8
StatePublished - Apr 2000

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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