Figure 1.

NF-κB signaling cascade. Nuclear factor-κB (NF-κB) activity is stimulated by canonical (classical) and noncanonical (alternative) pathways. The canonical pathway can be activated by extensive numbers of stimuli, such as lipopolysaccharide (LPS), antigens, and tumor-necrosis factor (TNF). The inhibitor of NF-κB (IκB) kinase (IKK) complex that comprises IKKα (IKK1), IKKβ (IKK2), and NF-κB essential modulator (NEMO, also known as IKKγ) is a point of convergence for the canonical pathway, which phosphorylates IκB proteins, allowing the cytoplasmic NF-κB to be released and to enter into the nucleus to elicit transcriptional activity. The noncanonical pathway responds to a different set of ligands, including CD40 ligand (CD40L) and B cell-activation factor (BAFF). Upon binding of these ligands to their cognate receptors, NF-κB-inducing kinase (NIK) specifically phosphorylates IKKα, which processes the p100 into mature p52. The p52 then translocates to the nucleus via its dimerization with RelB to activate noncanonical NF-κB target genes.