title: Signaling via the NFκB system.
abstract: The nuclear factor kappa B (NFκB) family of transcription factors is a key regulator of immune development, immune responses, inflammation, and cancer. The NFκB signaling system (defined by the interactions between NFκB dimers, IκB regulators, and IKK complexes) is responsive to a number of stimuli, and upon ligand-receptor engagement, distinct cellular outcomes, appropriate to the specific signal received, are set into motion. After almost three decades of study, many signaling mechanisms are well understood, rendering them amenable to mathematical modeling, which can reveal deeper insights about the regulatory design principles. While other reviews have focused on upstream, receptor proximal signaling (Hayden MS, Ghosh S. Signaling to NF-κB. Genes Dev 2004, 18:2195-2224; Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R. TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme. Cell Mol Life Sci 2008, 65:2964-2978), and advances through computational modeling (Basak S, Behar M, Hoffmann A. Lessons from mathematically modeling the NF-κB pathway. Immunol Rev 2012, 246:221-238; Williams R, Timmis J, Qwarnstrom E. Computational models of the NF-KB signalling pathway. Computation 2014, 2:131), in this review we aim to summarize the current understanding of the NFκB signaling system itself, the molecular mechanisms, and systems properties that are key to its diverse biological functions, and we discuss remaining questions in the field. WIREs Syst Biol Med 2016, 8:227-241. doi: 10.1002/wsbm.1331 For further resources related to this article, please visit the WIREs website.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Mitchell
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Jesse
authors.identifier: 0000-0002-3671-6778
authors.initials: J
authors.lastname: Vargas
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D019281:Dimerization; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D051550:I-kappa B Kinase