Figure 5.

Non-canonical NF-κB signaling pathway. (A) On ligand binding, receptors crosslink and the TRAF2:TRAF3:CIAP1/2 complex is recruited to the receptors. TRAF2 ubiquitinates cIAP1 and cIAP2, which then ubiquitinate TRAF3 (and TRAF2 to some extent) and stimulate its rapid degradation. NF-κB-inducing kinase (NIK) is released. TPL2 physically assembles with IKK and NIK and phosphorylates NIK which then phosphorylates and activates IKKα. TPL2 also activates IKKα. IKKα phosphorylates p100. Once phosphorylated, p100 is degraded by the proteasome and p52 is released and can dimerize and translocate to the nucleus. (B) Dimerization of TRAF3 with TRAF2 allows recruitment of the CIAPs1/2 ubiquitin ligases, Normally, NIK is bound by this complex and targeted for constant ubiquitination and proteasomal degradation. P, phosphate; U, ubiquitin.