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| Item Type: | Article |
|---|---|
| Title: | Sources of dynamic variability in NF-κB signal transduction: a mechanistic model |
| Creators Name: | Mothes, J. and Busse, D. and Kofahl, B. and Wolf, J. |
| Abstract: | The transcription factor NF-{kappa}B (p65/p50) plays a central role in the coordination of cellular responses by activating the transcription of numerous target genes. The precise role of the dynamics of NF-{kappa}B signalling in regulating gene expression is still an open question. Here, we show that besides external stimulation intracellular parameters can influence the dynamics of NF-{kappa}B. By applying mathematical modelling and bifurcation analyses, we show that NF-{kappa}B is capable of exhibiting different types of dynamics in response to the same stimulus. We identified the total NF-{kappa}B concentration and the I{kappa}B{alpha} transcription rate constant as two critical parameters that modulate the dynamics and the fold change of NF-{kappa}B. Both parameters might vary as a result of cell-to-cell variability. The regulation of the IκBα transcription rate constant, e.g. by co-factors, provides the possibility of regulating the NF-{kappa}B dynamics by crosstalk. |
| Keywords: | Bifurcation Analysis, Cell-to-Cell Variability, Fold Change, I{kappa}B{alpha} Transcription, Mathematical Model, Oscillations, Steady State |
| Source: | BioEssays |
| ISSN: | 0265-9247 |
| Publisher: | Wiley-Blackwell |
| Volume: | 37 |
| Number: | 4 |
| Page Range: | 452-462 |
| Date: | April 2015 |
| Official Publication: | https://doi.org/10.1002/bies.201400113 |
| PubMed: | View item in PubMed |
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