| Transcription factors of the nuclear factor κ B (NF-κB)/Rel family is a ubiquitously expressed transcription factor that regulates many cytokine and Ig genes. It is involved in immune, inflammatory, viral, and acute phase responses. There are five family members in mammals: RelA (p65), c-Rel, RelB, NF-κB1 (p105/p50) and NF-κB2 (p100/p52). The most studied NF-κB complex consists of the p50 and p65 subunits, both containing a 300 amino acid region with homology to the Rel proto-oncogene product. The p50 subunit binds DNA, whereas the p65 subunit is responsible for the interaction of NF-κB with its inhibitor, IκB. In most cell types, the p50/p65 heterodimer is located within the cytoplasm complexed to IκB. This complex prevents nuclear translocation and activity of NF-κB. In response to stimuli such as cytokines, LPS, and viral infections, IκB is phosphorylated at critical residues. This phosphorylation induces dissociation of the IκB/NF-κB complex, allowing the free heterodimeric NF-κB to form a heterotetramer that translocates to the nucleus. In the nucleus, it binds to the κB site within promoters and enhancers and functions as a transcriptional activator. |
