A Fourth Ikappab Protein Within the Nf-kappab Signaling Module.
From: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cell
- Publish Date: Jan 2007
- ISSN: 0092-8674
- Volume: 128
- Issue: 2
- Pages: 369-81
- Medium: Print
- Language: English
- Citation (JAMA): Basak Soumen, Kim Hana, Kearns Jeffrey D, et al. A Fourth Ikappab Protein Within the Nf-kappab Signaling Module.. Cell Jan 2007;128:369-81
Abstract
Inflammatory NF-kappaB/RelA activation is mediated by the three canonical inhibitors, IkappaBalpha, -beta, and -varepsilon. We report here the characterization of a fourth inhibitor, nfkappab2/p100, that forms two distinct inhibitory complexes with RelA, one of which mediates developmental NF-kappaB activation. Our genetic evidence confirms that p100 is required and sufficient as a fourth IkappaB protein for noncanonical NF-kappaB signaling downstream of NIK and IKK1. We develop a mathematical model of the four-IkappaB-containing NF-kappaB signaling module to account for NF-kappaB/RelA:p50 activation in response to inflammatory and developmental stimuli and find signaling crosstalk between them that determines gene-expression programs. Further combined computational and experimental studies reveal that mutant cells with altered balances between canonical and noncanonical IkappaB proteins may exhibit inappropriate inflammatory gene expression in response to developmental signals. Our results have important implications for physiological and pathological scenarios in which inflammatory and developmental signals converge.
Mesh Headings (Keywords): Animals, Binding Sites, Cell Line, Transformed, Computational Biology, Computer Simulation, Gene Expression Regulation, I-kappa B Kinase, I-kappa B Proteins, Inflammation, Macromolecular Substances, Mice, Mice, Knockout, NF-kappa B, NF-kappa B p50 Subunit, NF-kappa B p52 Subunit, NIH 3T3 Cells, Protein-Serine-Threonine Kinases, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 17254973
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.