Function
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.
Gene Ontology
GO:0005737; GO:0005829; GO:0005576; GO:0033256; GO:0005739; GO:0005654; GO:0005634; GO:0034774; GO:0035580; GO:0042805; GO:0003682; GO:0001228; GO:0003700; GO:0000981; GO:0001227; GO:0019899; GO:0042802; GO:0046982; GO:0042803; GO:0000980; GO:0000977; GO:0001225; GO:0008134; GO:0044212; GO:0000976; GO:0006915; GO:1904385; GO:0071359; GO:0071347; GO:0071354; GO:0071222; GO:0071260; GO:0071316; GO:0071356; GO:0038095; GO:0006954; GO:0070498; GO:0031293; GO:0043066; GO:0010956; GO:0032269; GO:0032375; GO:0010629; GO:0050728; GO:0045083; GO:0000122; GO:0010957; GO:0043312; GO:0090263; GO:1900127; GO:0010884; GO:0010744; GO:2000630; GO:0051092; GO:0045944; GO:0045893; GO:0032481; GO:0035994; GO:0002223; GO:0051403; GO:0050852; GO:0006366