[The Rel/NF-kappa-B transcription factors: complex role in cell regulation]

The transcription factor NF-kappa B has attracted widespread attention among researchers. NF-kappa B displays some original characteristics including rapid regulation, the wide range of genes that it controls and its probable involvement in several diseases. In resting cells, NF-kappa B is kept in an inactive form in the cytoplasm where it is bound to a member of the I kappa B family of inhibitory proteins. NF-kappa B can be activated by exposure of cells to physiological as well as non physiological stimuli. Upon cell activation, the inhibitors are modified through site specific phosphorylations which target them for subsequent ubiquitination and proteolytic degradation by the proteasome. Removal of the inhibitor unmasks the nuclear localization signals on subunits of NF-kappa B. Free NF-kappa B moves to the nucleus where it binds to target DNA elements and activate transcription of genes encoding proteins involved in immune responses, inflammation or cell proliferation. NF-kappa B could be considered as a co-ordinating element in the body's responses to situations of stress, infection or inflammation. A tight regulation of NF-kappa B seems to be crucial since a dysfunction could promote pathogenic processes including AIDS (acquired immunodeficiency syndrome), rheumatoid arthritis and cancer. Additionally, it will be important to understand the exact roles for NF-kappa B in regulating apoptosis. NF-kappa B is now regarded as a good therapeutic target and the development of specific inhibitors should lead in the next future to novel therapeutics.