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| Item Type: | Article |
|---|---|
| Title: | Controlling nuclear NF-κB dynamics by β-TrCP-insights from a computational model |
| Creators Name: | Benary, U. and Wolf, J. |
| Abstract: | The canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway regulates central processes in mammalian cells and plays a fundamental role in the regulation of inflammation and immunity. Aberrant regulation of the activation of the transcription factor NF-κB is associated with severe diseases such as inflammatory bowel disease and arthritis. In the canonical pathway, the inhibitor IκB suppresses NF-κB's transcriptional activity. NF-κB becomes active upon the degradation of IκB, a process that is, in turn, regulated by the β-transducin repeat-containing protein (β-TrCP). β-TrCP has therefore been proposed as a promising pharmacological target in the development of novel therapeutic approaches to control NF-κB's activity in diseases. This study explores the extent to which β-TrCP affects the dynamics of nuclear NF-κB using a computational model of canonical NF-κB signaling. The analysis predicts that β-TrCP influences the steady-state concentration of nuclear NF-κB, as well as changes characteristic dynamic properties of nuclear NF-κB, such as fold-change and the duration of its response to pathway stimulation. The results suggest that the modulation of β-TrCP has a high potential to regulate the transcriptional activity of NF-κB. |
| Keywords: | Mathematical Modelling, β-TrCP, NF-κB Signaling, Drug Target, Oscillation, Fold-Change, Area Under Curve, Ordinary Differential Equations |
| Source: | Biomedicines |
| ISSN: | 2227-9059 |
| Publisher: | MDPI |
| Volume: | 7 |
| Number: | 2 |
| Page Range: | 40 |
| Date: | 27 May 2019 |
| Official Publication: | https://doi.org/10.3390/biomedicines7020040 |
| PubMed: | View item in PubMed |
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