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Controlling Nuclear NF-κB Dynamics by β-TrCP—Insights from a Computational Model

Mathematical Modelling of Cellular Processes, Max Delbrück Center for Molecular Medicine, 13125 Berlin-Buch, Germany
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Biomedicines 2019, 7(2), 40; https://doi.org/10.3390/biomedicines7020040
Received: 8 April 2019 / Revised: 15 May 2019 / Accepted: 24 May 2019 / Published: 27 May 2019
(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches 2019)
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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. View Full-Text
Keywords: mathematical modelling; β-TrCP; NF-κB signaling; drug target; oscillation; fold-change; area under curve; ordinary differential equations mathematical modelling; β-TrCP; NF-κB signaling; drug target; oscillation; fold-change; area under curve; ordinary differential equations
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Benary, U.; Wolf, J. Controlling Nuclear NF-κB Dynamics by β-TrCP—Insights from a Computational Model. Biomedicines 2019, 7, 40.

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