The Regulatory Logic of the NF-κB Signaling System
- Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093
- Correspondence: ahoffmann{at}ucsd.edu
Abstract
NF-κB 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-κB 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-κB regulation at these different timescales. We distinguish between the regulation of NF-κB dimer formation and the regulation of NF-κB activity. Given the number of regulators and reactions involved, the NF-κB signaling system is capable of integrating a multitude of signals to tune NF-κB activity, signal dose responsiveness, and dynamic control. We discuss the prevailing mechanisms that mediate signaling cross talk.
Footnotes
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Editors: Louis M. Staudt and Michael Karin
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Additional Perspectives on NF-κB available at www.cshperspectives.org
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