Non-canonical NF-κB signaling pathway

The non-canonical NF-kappa B pathway is an important arm of NF-kappa B signaling that predominantly targets activation of the p52/RelB NF-kappa B complex. This pathway depends on the inducible processing of p100, a molecule functioning as both the precursor of p52 and a RelB-specific inhibitor. A central signaling component of the non-canonical pathway is NF-kappa B-inducing kinase (NIK), which integrates signals from a subset of TNF receptor family members and activates a downstream kinase, I kappa B kinase-kappa (IKK alpha), for triggering p100 phosphorylation and processing. A unique mechanism of NIK regulation is through its fate control: the basal level of NIK is kept low by a TRAF-cIAP destruction complex and signal-induced non-canonical NF-kappa B signaling involves NIK stabilization. Tight control of the fate of NIK is important, since deregulated NIK accumulation is associated with lymphoid malignancies.