istic feature shared by all members. Dimers are kept inactive through their association to one of the inhibitory IkB proteins. Ligand mediated activation of receptors and subsequent interactions with various adapter proteins leads to the activation of the IkB kinases (IKK). The IKK complex is composed of Chuk (known as Ikkalpha or 1), Ikbkb (known as Ikkbeta or 2) and the regulatory subunit Ikbkg (Ikkgamma or Nemo). In the canonical (classical) NF-kB pathway, activation of Ikbkb/Ikbkg leads to phosphorylation of the inhibitory IkBs, best exemplified by Nfkbia (IkBalpha). Phosphorylated Nfkbia is targeted for degradation and the released NF-kB dimer, primarily the RelA(p65)/Nfkb1(p50) complex, translocates to the nucleus to induce the activation of many target genes. Amongst them is Nfkbia which thus provides a negative regulatory feedback loop. The non-canonical (alternative) pathway is independent of Ikbkg (Nemo)  but dependent on Map3k14 (Nik or NF-kB inducing kinase) upstream of Chuk (Ikkalpha). Activated Chuk phosphorylates the Nfkb2 (p100) member of the NF-kB family which is then processed to p52, followed by the translocation of the Nfkb2(p52)/RelB complex to the nucleus. The two and probably not the only NF-kB pathways are elicited by ligand-receptor subsets of the tumor necrosis factor (Tnf) superfamilies of ligands and receptors, respectively. The canonical NF-kB pathway downstream but not exclusively of tumor necrosis factor signaling through receptor 1 is regarded as a paradigm of NF-kB signaling. The association of ligand activated receptors with particular adapter molecules upstream of NF-kB activation coupled to the combinatorial NF-kB dimer and dimer-IkB interactions, provides for a diversity of conduits that uniquely modulate the manifestations and outcomes of NF-kB pathway. To see the ontology report for annotations, GViewer and download, click here ...(less)