Controlling the Fate of NIK: A Central Stage in Noncanonical NF-κB Signaling

The noncanonical nuclear factor kappa B (NF-kappa B) pathway is a specific arm of NF-kappa B signaling that regulates important aspects of immune function. Activation of this pathway centers on the modulation of a pivotal signaling component: NF-kappa B-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-kappa B 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 kappa B (I kappa B) kinase alpha (IKK alpha), and degradation. Thus, controlling the fate of NIK is emerging as a central mechanism in noncanonical NF-kappa B signaling.