Nuclear 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.

NF-kB PROTEINS As most transcription factors, the mammalian NF-kB family has multiple members including RelA (p65), NF-kB1 (p50; p105), NF-kB2 (p52; p100), c-Rel, and RelB1 2 (fig 1). These proteins have a structurally conserved N-terminal 300-amino acid region, which contains the dimerisation, nuclear localisation, and DNA binding domains (see fig 1). The c-Rel, RelB, and RelA proteins also have a C-terminal nonhomologous transactivation domain that strongly activates transcription from NF-kB binding sites. On the other hand, the other Rel proteins, such as p50 homodimers, lack the transcription activation domain but still bind to kB-consensus sites and therefore function as transcription repressors. 3 The p50 and p52 proteins are generated by proteolytic processing of their precursors, p105 and p100, respectively. 4 All members of the NF-kB family except RelB can form homodimers, as well as heterodimers with one another. The most prevalent activated form of NF-kB is the heterodimer of subunit p65 associated with either subunit p50 or p52. In contrast, expression of RelB is restricted to specific regions of the thymus, lymph nodes, and Peyer’s patches. c-Rel is also confined to the haemopoietic cells and lymphocytes. The transcription of RelB, c-Rel, and p105 themselves is regulated by NF-kB.