This model corresponds to the IkB-NFkB signaling in wild type cells and reproduces the dynamics of the species as depicted in Figure 2 F of the paper. The authors mention that the simulation is carried out in three phases, where the steady state values of the species in one phase are fed to the succeding phase. This model captures the simulation dynamics of two phases and makes use of the event section to introduce the stimulus and thereby transition to the next phase. Accordingly, a few terms have been introduced that make this transition possible, this in no way compromises the original model. Also, the simulation plots are not an exact reproduction of the figures in the paper, they do however match the simulation results that the authors shared with us. Model was successfully tested on MathSBML.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
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The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation.
- Alexander Hoffmann, Andre Levchenko, Martin L Scott, David Baltimore
- Science (New York, N.Y.) , 11/ 2002 , Volume 298 , Issue 5596 , pages: 1241-1245 , PubMed ID: 12424381
- Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
- 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.
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modeller: Harish Dharuri
Metadata information
isDescribedBy (1 statement)
hasTaxon (1 statement)
isPartOf (2 statements)
KEGG Pathway T cell receptor signaling pathway - Mus musculus (mouse)
hasProperty (1 statement)
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