Nuclear factor (NF)-kB proteins: therapeutic targets*

N uclear factor (NF)-kB is a key player in the control of both innate and adaptive immunity. NF-kB proteins are present in the cytoplasm in association with inhibitory proteins called inhibitors of kB (IkBs). On activation by a large plethora of inducers, the IkB proteins are phosphorylated, ubiquitinated, and subsequently degraded in the proteasomes. Degradation of IkBs allows translocation of NF-kB into the nucleus and bind to their cognate DNA binding sites to regulate the transcription of large numbers of genes including antimicrobial peptides, cytokines, chemokines, stress response proteins, and antiapoptotic proteins. NF-kB activity is essential for lymphocyte survival, activation, and mounting normal immune responses. Constitutive activation of NF-kB pathways is often associated with inflammatory diseases like rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and asthma. Better understanding of the regulation of NF-kB will provide a platform for development of specific therapeutic agents targeted towards the inflammatory diseases.