The two faces of NFkappaB in cell survival responses.

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