Busse Matthew S, Arnold Christopher P, Towb Par, Katrivesis James, Wasserman Steven A
Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA 92093-0349, USA.
EMBO J. 2007 Aug 22;26(16):3826-35. doi: 10.1038/sj.emboj.7601798. Epub 2007 Jul 26.
The Toll and Imd pathways induce humoral innate immune responses in Drosophila by activating NF-kappaB proteins that bind kappaB target sites. Here, we delineate a kappaB site sequence code that directs pathway-specific expression of innate immune loci. Using bioinformatic analysis of expression and sequence data, we identify shared properties of Imd- and Toll-specific response elements. Employing synthetic kappaB sites in luciferase reporter and in vitro binding assays, we demonstrate that the length of the (G)(n) element in the 5' half-site and of the central (A,T)-rich region combine to specify responsiveness to one or both pathways. We also show that multiple sites function to enhance the response to either or both pathways. Together, these studies elucidate the mechanism by which kappaB motifs direct binding by particular Drosophila NF-kappaB family members and thereby induce specialized innate immune repertoires.
Toll和Imd信号通路通过激活与κB靶位点结合的NF-κB蛋白，在果蝇中诱导体液先天性免疫反应。在此，我们描绘了一种κB位点序列编码，其指导先天性免疫基因座的信号通路特异性表达。通过对表达和序列数据进行生物信息学分析，我们确定了Imd特异性和Toll特异性反应元件的共同特性。利用荧光素酶报告基因中的合成κB位点以及体外结合试验，我们证明了5'半位点中(G)(n)元件的长度和富含中央(A,T)区域的长度共同决定了对一种或两种信号通路的反应性。我们还表明，多个位点可增强对一种或两种信号通路的反应。这些研究共同阐明了κB基序指导特定果蝇NF-κB家族成员结合并由此诱导专门先天性免疫库的机制。
