A Toll-dependent Bre1/Rad6-cact feedback loop in controlling host innate immune response.

Cell reports 2022 Dec 13

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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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Qingshuang Cai, Huimin Guo, Rong Fang, Yongzhi Hua, Yangyang Zhu, Xianrui Zheng, Jing Yan, Jiale Wang, Yixuan Hu, Chuchu Zhang, Chao Zhang, Renjie Duan, Fanrui Kong, Shikun Zhang, Di Chen, Shanming Ji. A Toll-dependent Bre1/Rad6-cact feedback loop in controlling host innate immune response. Cell reports. 2022 Dec 13;41(11):111795