Controlling Nuclear NF-κB Dynamics by β-TrCP—Insights from a Computational Model
AbstractThe 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
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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.
Benary U, Wolf J. Controlling Nuclear NF-κB Dynamics by β-TrCP—Insights from a Computational Model. Biomedicines. 2019; 7(2):40.Chicago/Turabian Style
Benary, Uwe; Wolf, Jana. 2019. "Controlling Nuclear NF-κB Dynamics by β-TrCP—Insights from a Computational Model." Biomedicines 7, no. 2: 40.
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