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Overview
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Background
Transcription factors of the nuclear factor ? B (NF-?B)/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-?B1 (p105/p50) and NF-?B2 (p100/p52). The most studied NF-?B 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-?B with its inhibitor, I?B. In most cell types, the p50/p65 heterodimer is located within the cytoplasm complexed to I?B. This complex prevents nuclear translocation and activity of NF-?B. In response to stimuli such as cytokines, LPS, and viral infections, I?B is phosphorylated at critical residues. This phosphorylation induces dissociation of the I?B/NF-?B complex, allowing the free heterodimeric NF-?B to form a heterotetramer that translocates to the nucleus. In the nucleus, it binds to the ?B site within promoters and enhancers and functions as a transcriptional activator.
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