Figure 3.

Canonical and non-canonical signaling to NF-κB. The canonical pathway is, e.g., induced by TNFα, IL-1, or LPS and uses a large variety of signaling adaptors to engage IKK activity. Phosphorylation of serine residues in the signal responsive region (SRR) of classical IκBs by IKKβ leads to IκB ubiquitination and subsequent proteosomal degradation. This results in release of the NF-κB dimer, which can then translocate to the nucleus and induce transcription of target genes. The non-canonical pathway depends on NIK (NF-κB-inducing kinase) induced activation of IKKα. IKKα phosphorylates the p100 NF-κB subunit, which leads to proteosomal processing of p100 to p52. This results in the activation of p52-RelB dimers, which target specific κB elements.