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• W2106043531 abstract "Many cellular stress-responsive signaling systems exhibit highly dynamic behavior with oscillatory features mediated by delayed negative feedback loops. What remains unclear is whether oscillatory behavior is the basis for a signaling code based on frequency modulation (FM) or whether the negative feedback control modules have evolved to fulfill other functional requirements. Here, we use experimentally calibrated computational models to interrogate the negative feedback loops that regulate the dynamic activity of the transcription factor NF-B. Linear stability analysis of the model shows that oscillatory frequency is a hard-wired feature of the primary negative feedback loop and not a function of the stimulus, thus arguing against an FM signaling code. Instead, our modeling studies suggest that the two feedback loops may be tuned to provide for rapid activation and inactivation capabilities for transient input signals of a wide range of durations; by minimizing late phase oscillations response durations may be fine-tuned in a graded rather than quantized manner. Further, in the presence of molecular noise the dual delayed negative feedback system minimizes stochastic excursions of the output to produce a robust NF-B response." @default.
• W2106043531 created "2016-06-24" @default.
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• W2106043531 date "2013-06-27" @default.
• W2106043531 modified "2023-10-16" @default.
• W2106043531 title "Dual Delayed Feedback Provides Sensitivity and Robustness to the NF-κB Signaling Module" @default.
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• W2106043531 doi "https://doi.org/10.1371/journal.pcbi.1003112" @default.
• W2106043531 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3694842" @default.
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• W2106043531 hasPublicationYear "2013" @default.
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