The regulatory logic of the NF-kappaB signaling system.
NF-kappaB refers to multiple dimers of Rel homology domain (RHD) containing polypeptides, which are controlled by a stimulus-responsive signaling system that mediates the physiological responses to inflammatory intercellular cytokines, pathogen exposure, and developmental signals. The NF-kappaB signaling system operates on transient or short timescales, relevant to inflammation and immune responses, and on longer-term timescales relevant to cell differentiation and organ formation. Here, we summarize our current understanding of the kinetic mechanisms that allow for NF-kappaB regulation at these different timescales. We distinguish between the regulation of NF-kappaB dimer formation and the regulation of NF-kappaB activity. Given the number of regulators and reactions involved, the NF-kappaB signaling system is capable of integrating a multitude of signals to tune NF-kappaB activity, signal dose responsiveness, and dynamic control. We discuss the prevailing mechanisms that mediate signaling cross talk.
O'Dea
Ellen
E
Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
Hoffmann
Alexander
A
D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation; D008954:Models, Biological; D008957:Models, Genetic; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA