The two faces of NFκB in cell survival responses

Activation of NF kappa B is controlled by a diverse range of stimuli including growth factors, and apoptotic inducers, but paradoxically these stimuli seem to activate the same NF kappa B signaling pathways. In particular, growth factors leading to cell survival and DNA damaging agents leading to apoptosis seem to activate the same NF kappa B signaling pathway. Post-translational modifications of NF kappa B and surrounding histones give selective targeting of NF kappa B regulated genes contributing to cell survival or apoptosis. NF kappa B activation induces death receptor 5 (DR5) expression following DNA damaging agent etoposide treatment but not following growth factor EGF treatment. This differential expression is regulated by the recruitment of histone deacytelasse 1 (HDAC1) to the DR5 gene by NF kappa B following EGF treatment but not etoposide treatment. In addition, HDAC inhibitors induce NF kappa B binding to the DR5 gene and DR5 expression, contributing to HDAC inhibitor induced apoptosis. These findings provide a possible model for selective NF kappa B transcriptional regulation based upon the context of post-translational modifications in surrounding histones on NF kappa B regulated target genes.