NF-κB and IκB proteins. A schematic representation of various domains in (Rel)/nuclear factor of kappa B (NF-κB) proteins including the Rel Homology Domain, RHD, which comprises the DNA binding domain, nuclear localization signal (NLS), dimerization domains and the IκB binding domain. (Rel)/nuclear factor of κB (NF-κB) proteins include those that do not require proteolytic processing and those that do require proteolytic processing. The first group consists of: RelA (known as p65), c-Rel and RelB and the second group includes NF-κB1 (known as p105) and NF-κB2 (known as p100), which further produce p50 and p52 proteins, respectively. These two groups dimerize, the most commonly detected NF-κB dimer is p50 – RelA. RelA is responsible for most of NF-κB transcriptional activity due to the presence of a strong transcriptional activation domain. p50 – c-Rel dimers are less abundant. Both p50 – RelA and p50 – c-Rel dimers are regulated by interactions with the inhibitor of κB (IκB) proteins, which cause their cytoplasmic localization. RelB, however, mostly associates with p100 and the p100 – RelB dimers are exclusively cytoplasmic. Proteolytic processing of p100 results in the release of p52 – RelB dimers, which translocate to the nucleus. RelB, unlike RelA and c-Rel, can function as an activator or repressor (Reproduced with permission from Nature Reviews Cancer (Vol 2, No. 4, pp 301#150;310 copyright (2002) Macmillan Magazines Ltd.).