Dying for NF-κB?: Control of cell death by transcriptional regulation of the apoptotic machinery

The transcription factor nuclear factor kappaB (NF-kappaB) is a pleiotropic protein complex that is activated from a sequestered, cytoplasmic form by pro-inflammatory extracellular signals and cellular stress. Several hundred cellular genes have been shown to be regulated by NF-kappaB, including cytokines, chemokines and adhesion molecules. Nearly eight years ago, a flurry of publications showed that loss or suppression of NF-kappaB results in an enhanced sensitivity to apoptosis. In the ensuing years, activation of NF-kappaB has become almost synonymous with enhanced cell survival, although more recent data suggests that this transcription factor plays a more complex role in the regulation of cell death.