New insights into NF-κB regulation and function

NF-κB (nuclear factor-κB) transcription factors have multiple critical roles in the regulation of immune responses. In unstimulated cells, NF-κB proteins are sequestered in the cytoplasm by IκB inhibitory proteins. Various immune stimuli induce the IκB kinase (IKK) to phosphorylate IκBs, triggering their ubiquitination and proteasomal degradation, which permits nuclear translocation of associated NF-κB subunits and activation of NF-κB target genes. Recent studies have highlighted the importance of dynamic ubiquitination-deubiquitination events in regulating this canonical NF-κB signaling pathway. Ubiquitination additionally plays critical roles in activation of the noncanonical pathway that regulates NF-κB via signal-induced processing of NF-κB2 p100. New research has also identified several novel regulatory proteins that control the transcriptional activity of nuclear NF-κB.