FIGURE 3.

Canonical and non-canonical pathway leading to the activation of NF-κB. TRAF3 inhibits activation of the classical NFκB pathway A high level of TRAF3 interferes with the recruitment of TRAF2 to the receptor. In parallel, TRAF3 induces NIK degradation and consequently inhibits the activation of the alternative arm of NFκB. The activation of canonical pathway results in the phosphorylation of IκBαα by the IKK complex, leading to its ubiquitylation and subsequent degradation by the proteasome. The RelA/p50 complex is free to translocate to the nucleus to activate the transcription of target genes. The non-canonical pathway results in the NIK stabilization. In response to receptor crosslinking, TRAFs and cIAP1/2 are recruited to the receptor, where cIAP1/2 ubiquitinates TRAF2 and TRAF3 and stimulates their degradation. Accumulated NIK activates IKKα , which in turn phosphorylates p100, leading to p100 processing to p52, which can lead to the activation of p52-RelB that target distinct κB element and induce the transcription of target genes.