Controlling the fate of NIK: A central stage in noncanonical NF-κB signaling

The noncanonical nuclear factor κB (NF-κB) pathway is a specific arm of NF-κB signaling that regulates important aspects of immune function. Activation of this pathway centers on the modulation of a pivotal signaling component: NF-κB-inducing kinase (NIK). Under normal conditions, NIK undergoes constitutive degradation, which keeps its abundance below the threshold required for its function, and signal-induced activation of the noncanonical NF-κB pathway is coupled with the stabilization and accumulation of NIK. A study now shows that signal-induced accumulation of NIK is subject to feedback control, which involves its phosphorylation by a downstream kinase, inhibitor of κB (IκB) kinase α (IKKα), and degradation. Thus, controlling the fate of NIK is emerging as a central mechanism in noncanonical NF-κB signaling.