FIGURE 3.

Non-canonical NF-κB signaling. Non-canonical NF-κB signaling is initiated by the binding of cell surface receptors to their ligands. Trimerization of the receptors recruits TRAF2, cIAP1, and cIAP2 to the receptor. This changes the specificity of cIAP1/2 ubiquitin ligation from NIK to TRAF3. TRAF3 is ubiquitinated by this complex and degraded by the proteasome. The absence of TRAF3 prevents degradation of NIK, leading to its accumulation. NIK can phosphorylate IKKα. Activated IKKα phosphorylates p100, inducing its partial degradation by the proteasome. The processed p100 subunit, p52, associates with RelB and translocates into the nucleus where it mediates transcription of pro-survival genes.