Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 347, Issue -, Pages 44-53Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2014.01.015
Keywords
Mathematical modeling; Signalling pathways; Transcription factor dynamics; Oscillations
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Funding
- Intra-European Fellowships for career development [2011-298447]
- Italian AIRC [R0444]
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The mathematical modeling of the NF-kappa B oscillations has attracted considerable attention in recent times, but there is a lack of simple models in the literature that can capture the main features of the dynamics of this important transcription factor. For this reason we propose a simple model that summarizes the key steps of the NF-kappa B pathway. We show that the resulting 5-dimensional dynamical system can reproduce different phenomena observed in experiments. Our model can display smooth and spiky oscillations in the amount of nuclear NF-kappa B and can reproduce the variety of dynamics observed when different stimulations such as TNF-alpha and LPS are used. Furthermore we show that the model can be easily extended to reproduce the expression of early, intermediate and late genes upon stimulation. As a final example we show that our simple model can mimic the different transcriptional outputs observed when cells are treated with two different drugs leading to nuclear localization of NF-kappa B: Leptomycin B and Cycloheximide. (C) 2014 Elsevier Ltd. All rights reserved.
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