Dataset Information

Controlling Nuclear NF-?B Dynamics by ?-TrCP-Insights from a Computational Model.

ABSTRACT: The canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) 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-?B is associated with severe diseases such as inflammatory bowel disease and arthritis. In the canonical pathway, the inhibitor I?B suppresses NF-?B's transcriptional activity. NF-?B becomes active upon the degradation of I?B, a process that is, in turn, regulated by the ?-transducin repeat-containing protein (?-TrCP). ?-TrCP has therefore been proposed as a promising pharmacological target in the development of novel therapeutic approaches to control NF-?B's activity in diseases. This study explores the extent to which ?-TrCP affects the dynamics of nuclear NF-?B using a computational model of canonical NF-?B signaling. The analysis predicts that ?-TrCP influences the steady-state concentration of nuclear NF-?B, as well as changes characteristic dynamic properties of nuclear NF-?B, such as fold-change and the duration of its response to pathway stimulation. The results suggest that the modulation of ?-TrCP has a high potential to regulate the transcriptional activity of NF-?B.

SUBMITTER: Benary U

PROVIDER: S-EPMC6631534 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Benary Uwe U Wolf Jana J

Biomedicines 20190527 2

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 t ...[more]

PMID: 31137887

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Dataset Information

Controlling Nuclear NF-?B Dynamics by ?-TrCP-Insights from a Computational Model.

Publications

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

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