| Description: | NF-kappa-B has been detected in numerous cell types thatexpress cytokines, chemokines, growth factors, cell adhesionmolecules, and some acute phase proteins in health and in variousdisease states. NF-kappa-B is activated by a wide variety ofstimuli, such as cytokines, oxidant-free radicals, inhaledparticles, ultraviolet irradiation, and bacterial or viralproducts. Inappropriate activation of NF-kappa-B has been linked toinflammatory events associated with autoimmune arthritis, asthma,septic shock, lung fibrosis, glomerulonephritis, atherosclerosis,and AIDS. In contrast, complete and persistent inhibition ofNF-kappa-B has been linked directly to apoptosis, inappropriateimmune cell development, and delayed cell growth. NFKB1 (MIM164011) and NFKB2 encode p105 and p100 proteins that are processedto produce the active p50 and p52 NF-kappa-B subunits,respectively. However, the p100 and p105 proteins serve regulatoryfunctions and should not be considered exclusively as precursorforms. The most abundant activated form of NF-kappa-B is aheterodimer of the p50 or p52 subunit bound to the RELA subunit(MIM 164014). Other NF-kappa-B complexes, consisting of hetero- andhomodimers of p50, p52, RELA, REL (MIM 164910), and RELB (MIM604758), have also been detected. NF-kappa-B complexes areinhibited by I-kappa-B proteins, NFKBIA (MIM 164008) or NFKBIB (MIM604495), which inactivate NF-kappa-B by trapping it in thecytoplasm. Phosphorylation of serine residues on the I-kappa-Bproteins by the kinases IKBKA (CHUK; MIM 600664) or IKBKB (MIM603258) marks them for destruction via the ubiquitination pathway,thereby allowing activation of the NF-kappa-B complex. Theactivated NF-kappa-B complex translocates into the nucleus andbinds DNA at kappa-B-binding motifs, such as 5-prime GGGRNNYYCC3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R isan A or G purine; and Y is a C or T pyrimidine). For reviews, seeChen et al. (1999) [PubMed 9895331] and Baldwin (1996) [PubMed8717528]. |
| Synonym: | Nuclear factor NF-kappa-B p100 subunit, DNA-binding factor KBF2, H2TF1, Lymphocyte translocation chromosome 10 protein, Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2, Oncogene Lyt-10, Lyt10, Nuclear factor NF-kappa-B p52 subunit, NFKB2, LYT10 |
