NF-kappa B

From Wikipedia, the free encyclopedia

NF-kappa-B (nuclear factor-kappa B) is a protein complex that is a transcription factor. NF-kappa-B is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-kappa-B plays a key role in regulating the immune response to infection. Consistent with this role, incorrect regulation of nF-kappa-B has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-2kappa-B has also been implicated in processes of synaptic plasticity and memory.

NF-kappa-B's role in cancer and other diseases

NF-kappa-B is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. As such, many different types of human tumors have misregulated
NF-kappa-B: that is, NF-kappa-B is constitutively active. Active NF-kappa-B turns on the expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die. In tumor cells, NF-kappa-B is active either due to mutations in genes encoding the NF-kappa-B transcription factors themselves or in genes that control NF-kappa-B activity (such as IkappaB genes); in addition, some tumor cells secrete factors that cause NF-kappa-B to become active. Blocking NF-kappa-B can cause tumor cells to stop proliferating, to die, or to become more sensitive to the action of anti-tumor agents. Thus, NF-kappa-B is the subject of much active research among pharmaceutical companies as a target for anti-cancer therapy.

Because NF-kappa-B controls many genes involved in inflammation, it is not surprising that NF-kappa-B is found to be chronically active in many inflammatory diseases, such as inflammatory bowel disease, arthritis, sepsis, asthma, among others. Many natural products (including anti-oxidants) that have been promoted to have anti-cancer and anti-inflammatory activity have also been shown to inhibit NF-kappa-B. There is a controversial US patent (US patent 6,410,516)[18] that applies to the discovery and use of agents that can block NF-?B for therapeutic purposes. This patent is involved in several lawsuits, including Ariad v. Lilly. Recent work by Karin, Ben-Neriah and others has highlighted the importance of the connection between NF-kappa-B, inflammation, and cancer, and underscored the value of therapies that regulate the activity of NF-kappa-B.