[Kappa-B nuclear factor and apoptosis of cancerous cells]

The transcriptional factor NF-kappa B is a key regulator of many biological processes such as the immune response, inflammation, development, cell proliferation and apoptosis. We investigated the role of NF-kappa B in the regulation of the pro-apoptotic protein Bax. We observed increased Bax proteins expression in several cancer cell lines stably expressing a mutated I kappa B-alpha that blocks NF-kappa B activity. Transient transfection experiments showed that NF-kappa B inhibited p53-dependent transactivation of the bax promoter, but this effect was not released by concomitant expression of several cofactors including CBP/p300. We also identified, for the first time, an NF-kappa B binding site in the bax gene promoter but the mutation of this site did not affect NF-kappa B induced inhibition of transcription. The mechanisms responsible for NF-kappa B inhibition of the bax promoter thus remain to be elucidated.