A Toll-dependent Bre1/Rad6-cact feedback loop in controlling host innate immune response
A Toll-dependent Bre1/Rad6-cact feedback loop in controlling host innate immune response
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Toll 依赖性 Bre1/Rad6-cact 反馈回路控制宿主先天免疫反应
DOI：
10.1016/j.celrep.2022.111795
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发表时间：
2022-12-13
期刊：
影响因子：
8.8
通讯作者：
Ji, Shanming
中科院分区：
文献类型：
--
作者：
Cai, Qingshuang;Guo, Huimin;Ji, Shanming
Toll信号通路最初被鉴定为参与早期胚胎发生的控制。后来证明，它也是控制许多真核生物（包括人类）中抗菌肽表达的主要先天免疫途径的一部分;仙人掌是果蝇中该途径的重要负调节因子，被发现在免疫防御过程中与Toll依赖性激活过程平行诱导。我们感兴趣的这种双重作用的机制，并在这里提供的证据表明，在致病性刺激，背，果蝇Toll通路的转录因子之一，可以诱导E3连接酶Bre 1的表达。我们进一步表明，Bre 1复合物与E2 Rad 6单泛素化组蛋白H2 B，并促进仙人掌的转录，以实现Toll免疫反应的稳态。我们的研究表征了Toll信号依赖的调节机制，在管理果蝇的Toll通路。
The Toll signaling pathway was initially identified for its involvement in the control of early embryogenesis. It was later shown to be also part of a major innate immune pathway controlling the expression of anti-microbial peptides in many eukaryotes including humans; cactus, the essential negative regulator of this pathway in flies, was found to be induced in parallel to the Toll-dependent activation process during immune defenses. We were interested in the mechanisms of this dual effect and provide here evidence that upon pathogenic stimuli, dorsal, one of the transcription factors of the fly Toll pathway, can induce the expression of the E3 ligase Bre1. We further show that Bre1 complexes with the E2 Rad6 to mono-ubiquitinate histone H2B and to promote the transcription of cactus to achieve homeostasis of the Toll immune response. Our studies characterize a Toll signal-dependent regulatory machinery in governing the Toll pathway in Drosophila.