Downregulation of lipopolysaccharide response in drosophila by negative crosstalk between the AP1 and NF-κB signaling modules
Downregulation of lipopolysaccharide response in drosophila by negative crosstalk between the AP1 and NF-κB signaling modules
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DOI：
10.1038/ni1159
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发表时间：
2005-02-01
影响因子：
30.5
通讯作者：
Kim, YJ
中科院分区：
文献类型：
--
作者：
Kim, T;Yoon, J;Kim, YJ
IkappaB激酶（IKK）和Jun N-末端激酶（Jnk）信号传导模块在针对脂多糖和肽聚糖的先天免疫应答期间的免疫效应分子的合成中是重要的。然而，这些免疫反应的特异性和终止所需的调节机制尚不清楚。我们在这里表明，果蝇JNK和IKK通路之间发生串扰，导致彼此的活动下调。Jnk的抑制作用是通过果蝇激活蛋白1（AP 1）与转录因子NF-κ B激活的启动子结合介导的。这种结合导致组蛋白去乙酰化酶dHDAC 1募集到编码抗菌蛋白Attacin-A的基因的启动子，并导致组蛋白乙酰化含量的局部修饰。因此，AP 1通过募集脱乙酰酶复合物来终止一组NF-κ B靶基因的活化而充当阻遏物。
IkappaB kinase (IKK) and Jun N-terminal kinase (Jnk) signaling modules are important in the synthesis of immune effector molecules during innate immune responses against lipopolysaccharide and peptidoglycan. However, the regulatory mechanisms required for specificity and termination of these immune responses are unclear. We show here that crosstalk occurred between the drosophila Jnk and IKK pathways, which led to downregulation of each other's activity. The inhibitory action of Jnk was mediated by binding of drosophila activator protein 1 (AP1) to promoters activated by the transcription factor NF-kappaB. This binding led to recruitment of the histone deacetylase dHDAC1 to the promoter of the gene encoding the antibacterial protein Attacin-A and to local modification of histone acetylation content. Thus, AP1 acts as a repressor by recruiting the deacetylase complex to terminate activation of a group of NF-kappaB target genes.