Regulation of the transcriptional activity of the nuclear factor-kappaB p65 subunit

Nuclear factor-kappaB (NF-kappaB) is well known for its role in inflammation, immune response, control of cell division and apoptosis. The function of NF-kappaB is primarily regulated by IkappaB family members, which ensure cytoplasmic localisation of the transcription factor in the resting state. Upon stimulus-induced IkappaB degradation, the NF-kappaB complexes move to the nucleus and activate NF-kappaB-dependent transcription. Over the years, a second regulatory mechanism, independent of IkappaB, has become generally accepted. Changes in NF-kappaB transcriptional activity have been assigned to phosphorylation of the p65 subunit by a large variety of kinases in response to different stimuli. Here, we give an overview of the kinases and signalling pathways mediating this process and comment on the players involved in tumour necrosis factor-induced regulation of NF-kappaB transcriptional activity. Additionally, we describe how other posttranslational modifications, such as acetylation and methylation of transcription factors or of the chromatin environment, may also affect NF-kappaB transcriptional activity.