Abstract
The NF-κB transcription factor has been shown to inhibit apoptosis in several experimental systems. We therefore investigated whether the expression of the Bax proapoptotic protein could be influenced by NF-κB activity. Increased Bax protein expression was detected in HCT116, OVCAR-3 and MCF7 cells stably expressing a mutated unresponsive IκB-α inhibitory protein that blocks NF-κB activity. Northern blots showed that bax mRNA expression was increased as a consequence of mutated IκB-α expression in HCT116 cells. A careful examination of the human bax gene promoter sequence showed three putative binding sites for NF-κB, and the κB2 site at position -687 could indeed bind NF-κB complexes in vitro. Transient transfection of a bax promoter luciferase construct in HCT116 cells showed that NF-κB proteins could partially inhibit the transactivation of the bax promoter by p53. Mutations or deletions of the κB sites, including κB2, indicated that this NF-κB-dependent inhibitory effect did not require NF-κB DNA-binding, and was thus an indirect effect. However, cotransfection of expression vectors for several known cofactors failed to identify a competition between p53 and NF-κB for a transcription coactivator. Our findings thus demonstrate for the first time that NF-κB regulates, through an indirect pathway, the bax gene expression.
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Abbreviations
- NF-κB:
-
Nuclear Factor-κB
- IκB:
-
inhibitor of κB
- TNF:
-
tumor necrosis factor
- EMSA:
-
electrophoretic mobility shift assay
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Acknowledgements
M-P Merville and C Van Lint are Research Associates and V Bours is a Senior Research Associate at the National Fund for Scientific Research (FNRS, Belgium). P Viatour is supported by a Télévie fellowship (FNRS, Belgium). This research was supported by grants from the ‘Centre Anti-Cancéreux’ (Liège, Belgium), the FRSM (Belgium) and from the ‘Concerted Action Program convention 97/02-214’, Communauté Française de Belgique.
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Bentires-Alj, M., Dejardin, E., Viatour, P. et al. Inhibition of the NF-κB transcription factor increases Bax expression in cancer cell lines. Oncogene 20, 2805–2813 (2001). https://doi.org/10.1038/sj.onc.1204343
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DOI: https://doi.org/10.1038/sj.onc.1204343
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