ODea2007 - A homeostatic model of IκB metabolism to control constitutive NF-κB activity
Questions concerning the paper should be addressed to the corresponding author. Alexander Hoffmann (email@example.com)
The original model was written and simulated within MathWorks MatLab 2006a using the ode15s (stiff/NDF) solver. It is highly recommended that those wanting to model this system use the MatLab version which we will freely provide upon request. As always, simulation results vary according to the numerical solver used.
Translation to SBML Level 2.1 was performed via reconstruction of the model within MathWorks SimBiology Desktop (version 2.1) followed by an Export to SBML.
- A homeostatic model of IkappaB metabolism to control constitutive NF-kappaB activity.
- O'Dea EL, Barken D, Peralta RQ, Tran KT, Werner SL, Kearns JD, Levchenko A, Hoffmann A
- Molecular Systems Biology , 0/ 2007 , Volume 3 , pages: 111 , PubMed ID: 17486138
- Signaling Systems Laboratory, Department of Chemistry and Biochemistry, UCSD, La Jolla, CA 92037, USA.
- Cellular signal transduction pathways are usually studied following administration of an external stimulus. However, disease-associated aberrant activity of the pathway is often due to misregulation of the equilibrium state. The transcription factor NF-kappaB is typically described as being held inactive in the cytoplasm by binding its inhibitor, IkappaB, until an external stimulus triggers IkappaB degradation through an IkappaB kinase-dependent degradation pathway. Combining genetic, biochemical, and computational tools, we investigate steady-state regulation of the NF-kappaB signaling module and its impact on stimulus responsiveness. We present newly measured in vivo degradation rate constants for NF-kappaB-bound and -unbound IkappaB proteins that are critical for accurate computational predictions of steady-state IkappaB protein levels and basal NF-kappaB activity. Simulations reveal a homeostatic NF-kappaB signaling module in which differential degradation rates of free and bound pools of IkappaB represent a novel cross-regulation mechanism that imparts functional robustness to the signaling module.
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer
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