Dual delayed feedback provides sensitivity and robustness to the NF-κB signaling module.

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-κB. 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 sugge

SUBMITTER: Longo DM 

PROVIDER: S-EPMC3694842 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature