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The IκB-NF-κB Signaling Module: Temporal Control and Selective Gene Activation

Science  08 Nov 2002:
Vol. 298, Issue 5596, pp. 1241-1245
DOI: 10.1126/science.1071914

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Abstract

Nuclear localization of the transcriptional activator NF-κB (nuclear factor κB) is controlled in mammalian cells by three isoforms of NF-κB inhibitor protein: IκBα, -β, and -ɛ. Based on simplifying reductions of the IκB–NF-κB signaling module in knockout cell lines, we present a computational model that describes the temporal control of NF-κB activation by the coordinated degradation and synthesis of IκB proteins. The model demonstrates that IκBα is responsible for strong negative feedback that allows for a fast turn-off of the NF-κB response, whereas IκBβ and -ɛ function to reduce the system's oscillatory potential and stabilize NF-κB responses during longer stimulations. Bimodal signal-processing characteristics with respect to stimulus duration are revealed by the model and are shown to generate specificity in gene expression.

  • * These authors contributed equally to this work.

  • Present address: Biogen, Incorporated, Cambridge, MA 02142, USA.

  • To whom correspondence should be addressed. E-mail: baltimo{at}caltech.edu

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