Silverman N, Zhou R, Stöven S, Pandey N, Hultmark D, Maniatis T
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Genes Dev. 2000 Oct 1;14(19):2461-71. doi: 10.1101/gad.817800.
Here we report the identification of a Drosophila IkappaB kinase complex containing DmIKKbeta and DmIKKgamma, homologs of the human IKKbeta and IKKgamma proteins. We show that this complex is required for the signal-dependent cleavage of Relish, a member of the Rel family of transcriptional activator proteins, and for the activation of antibacterial immune response genes. In addition, we find that the activated DmIKK complex, as well as recombinant DmIKKbeta, can phosphorylate Relish in vitro. Thus, we propose that the Drosophila IkappaB kinase complex functions, at least in part, by inducing the proteolytic cleavage of Relish. The N terminus of Relish then translocates to the nucleus and activates the transcription of antibacterial immune response genes. Remarkably, this Drosophila IkappaB kinase complex is not required for the activation of the Rel proteins Dif and Dorsal through the Toll signaling pathway, which is essential for antifungal immunity and dorsoventral patterning during early development. Thus, a yet to be identified IkappaB kinase complex must be required for Rel protein activation via the Toll signaling pathway.
我们在此报告，鉴定出一种果蝇IκB激酶复合物，其包含人IKKβ和IKKγ蛋白的同源物DmIKKβ和DmIKKγ。我们表明，该复合物对于转录激活蛋白Rel家族成员Relish的信号依赖性切割以及抗菌免疫反应基因的激活是必需的。此外，我们发现活化的DmIKK复合物以及重组DmIKKβ在体外可磷酸化Relish。因此，我们提出果蝇IκB激酶复合物至少部分地通过诱导Relish的蛋白水解切割发挥作用。Relish的N末端随后转位至细胞核并激活抗菌免疫反应基因的转录。值得注意的是，通过Toll信号通路激活Rel蛋白Dif和Dorsal时，不需要这种果蝇IκB激酶复合物，而Toll信号通路对于早期发育过程中的抗真菌免疫和背腹模式形成至关重要。因此，通过Toll信号通路激活Rel蛋白必定需要一种尚未鉴定的IκB激酶复合物。
