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.
Sun
Shao-Cong
SC
Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, TX 77030, USA. ssun@mdanderson.org
D000818:Animals; D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000097782:NF-kappaB-Inducing Kinase
D051550:I-kappa B Kinase; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase