Nuclear factor (NF)-κB proteins:: therapeutic targets

Nuclear factor (NF)-kappaB is a key player in the control of both innate and adaptive immunity. NF-kappaB proteins arc present in the cytoplasm in association with inhibitory proteins called inhibitors of kappaB (IkappaBs). On activation by a large plethora of inducers, the IkappaB proteins are phosphorylated, ubiquitinated, and subsequently degraded in the proteasomes. Degradation of IkappaBs allows translocation of NF-kappaB 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-kappaB activity is essential for lymphocyte survival, activation, and mounting normal immune responses. Constitutive activation of NF-kappaB pathways is often associated with inflammatory diseases like rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and asthma. Better understanding of the regulation of NF-kappaB will provide a platform for development of specific therapeutic agents targeted towards the inflammatory diseases.