Innate link between NF-kappaB activity and ubiquitin-like modifiers.

Among the several signalling pathways regulated by ubiquitin and ubiquitin-like proteins, the one activating NF-kappaB (nuclear factor kappaB) is certainly one of the best characterized. The regulation of the activity of this transcription factor by members of the ubiquitin family occurs at various levels, imposing overlapping controls of security of intriguing complexity. The formation of active macromolecular complexes such as the IKK [IkappaB (inhibitory kappaB) kinase] complex is tightly regulated by these post-translational modifications probably due to the fact that many signals converge on this signal's roundabout. An additional, very important level of NF-kappaB control occurs through the partial or total proteolysis of precursor and inhibitor molecules exerted by the ubiquitin-proteasome pathway. Regulation at this level implicates various conjugating and de-conjugating activities for ubiquitin, SUMO (small ubiquitin-related modifier) and NEDD8. Here, we summarize some of these events and underline the importance of the interconnecting ubiquitin and ubiquitin-like conjugating pathways that determine the status of the activity of this critical transcription factor.