Figure 4. In the absence of tumour necrosis factor (TNF), cellular inhibitor of apoptosis 1 (cIAP1) constitutively suppresses nuclear factor-kappa-B (NF-κB)-inducing kinase (NIK) abundance.

In cells that have not been exposed to cytokines, a complex containing cIAP1, TNF receptor-associated factor 2 (TRAF2), and TRAF3 interacts with NIK, causing it to be ubiquitilated and degraded, so that steady-state levels of NIK are very low. When cIAP1 is depleted by addition of an IAP antagonist compound or when genes for cIAP1 or TRAF2 are deleted, NIK levels rise, leading to cleavage and activation of the non-canonical NF-κB member p100/NF-κB2 by generation of the active product, p52. TNFR1, TNF receptor 1.