NF-κB 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-κB 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. The heterodimeric p65-p50 complex is the most abundant complex. The dimers bind at κB sites in the DNA of their target genes and the individual dimers have distinct preferences for different κB sites that they can bind with distinguishable affinity and specificity.
Different dimer combinations act as transcriptional activators or repressors, respectively. NF-κB complexes are held in the cytoplasm in an inactive state complexed with members of the NF-κB inhibitor (I-κB) family. In a conventional activation pathway, I-κB is phosphorylated by I-κB kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-κB complex which translocates to the nucleus. NF-κB heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-κB p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-κB complex.