PerspectiveNF-κB Signaling

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

Science Signaling  25 May 2010:
Vol. 3, Issue 123, pp. pe18
DOI: 10.1126/scisignal.3123pe18

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Abstract

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.

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