New insights into NF-κB regulation and function

NF-kappa B (nuclear factor-kappa B) transcription factors have multiple critical roles in the regulation of immune responses. In unstimulated cells, NF-kappa B proteins are sequestered in the cytoplasm by I kappa B inhibitory proteins. Various immune stimuli induce the I kappa B kinase (IKK) to phosphorylate I kappa Bs, triggering their ubiquitination and proteasomal degradation, which permits nuclear translocation of associated NF-kappa B subunits and activation of NF-kappa B target genes. Recent studies have highlighted the importance of dynamic ubiquitination-deubiquitination events in regulating this canonical NF-kappa B signaling pathway. Ubiquitination additionally plays critical roles in activation of the noncanonical pathway that regulates NF-kappa B via signal-induced processing of NF-kappa B2 p100 New research has also identified several novel regulatory proteins that control the transcriptional activity of nuclear NF-kappa B.