NF-B members and NF-B signaling. The NF-B family is composed of five related transcription factors: p50, p52, RelA (p65), c-Rel, and Rel-B. These transcription factors are related through homology domains in which they form homodimers and heterodimers that bind NF-B DNA sites, thus modulating gene expression. P50 and p52 are derived from p105 and p100 precursors, respectively. NF-B is silenced by interactions with inhibitory IkB family members in the cytoplasm. There are two NF-B signaling pathways known as the canonical pathway (or classical) and the noncanonical (or alternative) pathway. In both pathways, IkB kinase is activated and induces proteasomal degradation of the IkB inhibitor, thus allowing the translocation of the transcription factor subunits into the nucleus and induce transcription of target genes. BCR crosslinking provides the canonical NF-B signal and p100 production, while BLys receptor induce accumulation of p52, a protein deriving from p100 that activates NF-B 2 via the noncanonical pathway.
