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The IκB-NF-κB Signaling Module: Temporal Control and Selective Gene Activation
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.
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Metadata
- Authors
- Hoffmann, A., Levchenko, A., Scott, M. L., & Baltimore, D.
- Venue
- Science
- Published
- 2002-11-08
- Volume
- 298
- Issue
- 5596
- Pages
- 1241-1245
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1641228030
- Cited by
- 1,858
- References
- 2
- FWCI
- 24.36
- Type
- journal article
- Language
- en
- Open access
- closed
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