Cai Qingshuang, Guo Huimin, Fang Rong, Hua Yongzhi, Zhu Yangyang, Zheng Xianrui, Yan Jing, Wang Jiale, Hu Yixuan, Zhang Chuchu, Zhang Chao, Duan Renjie, Kong Fanrui, Zhang Shikun, Chen Di, Ji Shanming
Center for Developmental Biology, School of Life Sciences, Anhui Agricultural University, Hefei 230036, Anhui, China.
Center for Biological Technology, Anhui Agricultural University, Hefei 230036, Anhui, China.
Cell Rep. 2022 Dec 13;41(11):111795. doi: 10.1016/j.celrep.2022.111795.
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.
Toll信号通路最初因其参与早期胚胎发育的调控而被发现。后来发现它也是许多真核生物（包括人类）中控制抗菌肽表达的主要先天免疫途径的一部分；仙人掌蛋白是果蝇中该途径的关键负调节因子，发现在免疫防御过程中，它与Toll依赖性激活过程同时被诱导。我们对这种双重作用的机制感兴趣，并在此提供证据表明，在病原体刺激下，果蝇Toll途径的转录因子之一背蛋白可以诱导E3连接酶Bre1的表达。我们进一步表明，Bre1与E2 Rad6形成复合物使组蛋白H2B单泛素化，并促进仙人掌蛋白的转录，以实现Toll免疫反应的稳态。我们的研究描述了果蝇中控制Toll途径的Toll信号依赖性调节机制。
