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- Title
The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation.
- Authors
Hoffmann, Alexander; Levchenko, Andre; Scott, Martin L; Baltimore, David
- 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.
- Publication
Science (New York, N.Y.), 2002, Vol 298, Issue 5596, p1241
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1071914