The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation
- PMID: 12424381
- DOI: 10.1126/science.1071914
The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation
Abstract
Nuclear localization of the transcriptional activator NF-kappaB (nuclear factor kappaB) is controlled in mammalian cells by three isoforms of NF-kappaB inhibitor protein: IkappaBalpha, -beta, and - epsilon. Based on simplifying reductions of the IkappaB-NF-kappaB signaling module in knockout cell lines, we present a computational model that describes the temporal control of NF-kappaB activation by the coordinated degradation and synthesis of IkappaB proteins. The model demonstrates that IkappaBalpha is responsible for strong negative feedback that allows for a fast turn-off of the NF-kappaB response, whereas IkappaBbeta and - epsilon function to reduce the system's oscillatory potential and stabilize NF-kappaB 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.
Comment in
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Signal transduction. Decoding NF-kappaB signaling.Science. 2002 Nov 8;298(5596):1189-90. doi: 10.1126/science.1079331. Science. 2002. PMID: 12424362 No abstract available.
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