详细记录  
题名:A fourth IkappaB protein within the NF-kappaB signaling module.
作者:Basak S, Kim H, Kearns JD, Tergaonkar V, O Dea E, Werner SL, Benedict CA, Ware CF, Ghosh G, Verma IM, Hoffmann A.
来源:Cell[IF=29.431]. 2007 Jan 26;128(2):369-81.
URL :http://dx.doi.org/10.1016/j.cell.2006.12.033
日期:070415
摘要: Soumen Basak1, 2, Hana Kim1, 2, Jeffrey D. Kearns1, 2, Vinay Tergaonkar3, 5, Ellen O Dea1, 2, Shannon L. Werner1, 2, Chris A. Benedict4, Carl F. Ware4, Gourisankar Ghosh1, Inder M. Verma3 and Alexander Hoffmann1, 2, ,

1Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
2Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
3Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
4La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA

Received 11 March 2006; revised 6 July 2006; accepted 21 December 2006. Published: January 25, 2007. Available online 25 January 2007.

Summary

Inflammatory NF-B/RelA activation is mediated by the three canonical inhibitors, IB, -, and -. We report here the characterization of a fourth inhibitor, nfb2/p100, that forms two distinct inhibitory complexes with RelA, one of which mediates developmental NF-B activation. Our genetic evidence confirms that p100 is required and sufficient as a fourth IB protein for noncanonical NF-B signaling downstream of NIK and IKK1. We develop a mathematical model of the four-IB-containing NF-B signaling module to account for NF-B/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 IB 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. 3:

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