Dual Delayed Feedback Provides Sensitivity and Robustness to the NF-κB Signaling Module

Dual Delayed Feedback Provides Sensitivity and Robustness to the NF-κB Signaling Module

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 exper...

IκBɛ provides negative feedback to control NF-κB oscillations, signaling dynamics, and inflammatory gene expression

NF-kappaB signaling is known to be critically regulated by the NF-kappaB-inducible inhibitor protein IkappaBalpha. The resulting negative feedback has been shown to produce a propensity for oscillations in NF-kappaB activity. We report integrated experimental and computational studies that demonstrate that another IkappaB isoform, IkappaBepsilon, also provides negative feedback on NF-kappaB act...

A Fourth IκB Protein within the NF-κB Signaling Module

Soumen Basak, Hana Kim, Jeffrey D. Kearns, Vinay Tergaonkar, Ellen O’Dea, Shannon L. Werner, Chris A. Benedict, Carl F. Ware, Gourisankar Ghosh, Inder M. Verma, and Alexander Hoffmann* Department of Chemistry and Biochemistry Signaling Systems Laboratory University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Laboratory of Genetics, Salk Institute for Biological Studies,...

NF-κB signaling.

The NF-κB transcription factor is a critical regulator of the immune system, and is responsive to a large number of stimuli. Different stimuli engage signaling pathways to activate NF-κB, and effect distinct cellular responses. Mathematical modeling of the NF-κB network has been useful in studying the dynamic and cross-talk regulation of NF-κB. In this review, we discuss the regulation of NF-κB...

SnapShot: NF-κB Signaling Pathways