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The IkB–NF-kB Signaling Module: Temporal Control and Selective Gene Activation

Hoffmann, Alexander and Levchenko, Andre and Scott, Martin L. and Baltimore, David (2002) The IkB–NF-kB Signaling Module: Temporal Control and Selective Gene Activation. Science, 298 (5596). pp. 1241-1245. ISSN 0036-8075. doi:10.1126/science.1071914.

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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.

Item Type:Article
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Baltimore, David0000-0001-8723-8190
Additional Information:© 2002 American Association for the Advancement of Science. 15 March 2002; accepted 28 August 2002. The authors thank T. L. Johnson, S. Sanjabi, S. Smale, R. Tanaka, and an anonymous reviewer for suggestions on the manuscript. A.H. gratefully acknowledges the Jane Coffin Child Foundation for Cancer Research for postdoctoral fellowship support.
Funding AgencyGrant Number
Jane Coffin Child FoundationUNSPECIFIED
Issue or Number:5596
Record Number:CaltechAUTHORS:20141119-073353518
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Official Citation:The IκB-NF-κB Signaling Module: Temporal Control and Selective Gene Activation Alexander Hoffmann, Andre Levchenko, Martin L. Scott, and David Baltimore Science 8 November 2002: 298 (5596), 1241-1245. [DOI:10.1126/science.1071914]
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51931
Deposited By: Ruth Sustaita
Deposited On:19 Nov 2014 17:18
Last Modified:10 Nov 2021 19:17

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