Controlling the fate of NIK: a central stage in noncanonical NF-kappaB signaling.

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