FIGURE 2.

Canonical NF-κB signaling. Canonical NF-κB signaling is activated by the binding of extracellular ligands. Each receptor family differs in the upstream signaling molecules used to mediate signaling, but they share activation of TRAF2 and TRAF6. The TRAFs ubiquitinate TAK1, causing TAK1 to be activated and associate with IKKγ. TAK1 can then phosphorylate IKKβ, which in turn phosphorylates IκBα. Phosphorylated IκBα is degraded by the proteasome, releasing the canonical transcription factors p65, p50, and cREL. These translocate into the nucleus and activate pro-survival and pro-inflammatory genes.