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Controlling nuclear NF-κB dynamics by β-TrCP-insights from a computational model

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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
Page Range:40
Date:27 May 2019
Official Publication:https://doi.org/10.3390/biomedicines7020040
PubMed:View item in PubMed

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