title: IκBβ enhances the generation of the low-affinity NFκB/RelA homodimer.
abstract: The NFκB family of dimeric transcription factors regulate inflammatory and immune responses. While the dynamic control of NFκB dimer activity via the IκB-NFκB signalling module is well understood, there is little information on how specific dimer repertoires are generated from Rel family polypeptides. Here we report the iterative construction-guided by in vitro and in vivo experimentation-of a mathematical model of the Rel-NFκB generation module. Our study reveals that IκBβ has essential functions within the Rel-NFκB generation module, specifically for the RelA:RelA homodimer, which controls a subset of NFκB target genes. Our findings revise the current dogma of the three classical, functionally related IκB proteins by distinguishing between a positive 'licensing' factor (IκBβ) that contributes to determining the available NFκB dimer repertoire in a cell's steady state, and negative feedback regulators (IκBα and -ɛ) that determine the duration and dynamics of the cellular response to an inflammatory stimulus.
authors.affiliation: Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|The San Diego Center for Systems Biology, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M/C 0375,La Jolla, California, 92093-0375.
authors.forename: Rachel
authors.initials: R
authors.lastname: Tsui
authors.affiliation: Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M/C 0375,La Jolla, California, 92093-0375.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kearns
authors.affiliation: Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M/C 0375,La Jolla, California, 92093-0375.
authors.forename: Candace
authors.initials: C
authors.lastname: Lynch
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M/C 0375,La Jolla, California, 92093-0375.
authors.forename: Don
authors.initials: D
authors.lastname: Vu
authors.affiliation: Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|The San Diego Center for Systems Biology, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M/C 0375,La Jolla, California, 92093-0375.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Ngo
authors.affiliation: Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M/C 0375,La Jolla, California, 92093-0375.
authors.forename: Soumen
authors.initials: S
authors.lastname: Basak
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M/C 0375,La Jolla, California, 92093-0375.
authors.forename: Gourisankar
authors.initials: G
authors.lastname: Ghosh
authors.affiliation: Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|The San Diego Center for Systems Biology, University of California, San Diego, 9500 Gilman Dr M/C 0375, La Jolla, California, 92093-0375.|Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr M/C 0375,La Jolla, California, 92093-0375.|Department of Microbiology, Immunology and Molecular Genetics (MIMG), Institute for Quantitative and Computational Biosciences (QCB), University of California, Los Angeles, California, 90095.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D055592:Biophysical Phenomena; D020672:I-kappa B Proteins / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D055503:Protein Multimerization; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D020033:Protein Isoforms; D051996:Transcription Factor RelA