Dataset Information

Werner2005_IkappaB_kinase

ABSTRACT: This is the model described in the article: Stimulus specificity of gene expression programs determined by temporal control of IKK activity. by Werner SL, Barken D, Hoffmann A. Science. 2005 Sep 16;309(5742):1857-61; PMID: 16166517 , DOI= 10.1126/science.1113319 Abstract: A small number of mammalian signaling pathways mediate a myriad of distinct physiological responses to diverse cellular stimuli. Temporal control of the signaling module that contains IkappaB kinase (IKK), its substrate inhibitor of NF-kappaB (IkappaB), and the key inflammatory transcription factor NF-kappaB can allow for selective gene activation. We have demonstrated that different inflammatory stimuli induce distinct IKK profiles, and we examined the underlying molecular mechanisms. Although tumor necrosis factor-alpha (TNFalpha)-induced IKK activity was rapidly attenuated by negative feedback, lipopolysaccharide (LPS) signaling and LPS-specific gene expression programs were dependent on a cytokine-mediated positive feedback mechanism. Thus, the distinct biological responses to LPS and TNFalpha depend on signaling pathway-specific mechanisms that regulate the temporal profile of IKK activity. The model was implemented according to the description in the supplemental materials and by comparison to the matlab files provided by Prof. Hoffmann. It includes a delay for the induced transcription of IκBε mRNA. For the IKK input one of the randomly generated profiles was used. In its current form the model could not reproduce the time courses given in the article, as first the IKK activity profiles cannot easily be described by the same fitting functions in SBML and second the time delay limits simulation to tools, for which the current converters do not provide full SBML export. Originally created by libAntimony v1.4 (using libSBML 3.4.1) This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. 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.

SUBMITTER: Lukas Endler

PROVIDER: MODEL1008110000 | BioModels | 2005-01-01

REPOSITORIES: BioModels

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			Action	DRS
	MODEL1008110000?filename=MODEL1008110000-biopax2.owl	Owl
	MODEL1008110000?filename=MODEL1008110000-biopax3.owl	Owl
	MODEL1008110000?filename=MODEL1008110000.m	Other
	MODEL1008110000?filename=MODEL1008110000.pdf	Pdf
	MODEL1008110000?filename=MODEL1008110000.png	Other

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Publications

Stimulus specificity of gene expression programs determined by temporal control of IKK activity.

Werner Shannon L SL Barken Derren D Hoffmann Alexander A

Science (New York, N.Y.) 20050901 5742

A small number of mammalian signaling pathways mediate a myriad of distinct physiological responses to diverse cellular stimuli. Temporal control of the signaling module that contains IkappaB kinase (IKK), its substrate inhibitor of NF-kappaB (IkappaB), and the key inflammatory transcription factor NF-kappaB can allow for selective gene activation. We have demonstrated that different inflammatory stimuli induce distinct IKK profiles, and we examined the underlying molecular mechanisms. Although ...[more]

PMID: 16166517

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