Bacterial effector restricts liquid-liquid phase separation of ZPR1 to antagonize host UPRER.

Xiaoxiao Ouyang, Xueyun Wang, Pan Li, Qin Huang, Li Zhou, Jingxiang Li, Li Gao, Qi Sun, Fangni Chai, Shupan Guo, Zhihui Zhou, Xin Liu, Lunzhi Dai, Wei Cheng, Haiyan Ren

Cell reports 2023 Jul 25

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How pathogens manipulate host UPRER to mediate immune evasion is largely unknown. Here, we identify the host zinc finger protein ZPR1 as an interacting partner of the enteropathogenic E. coli (EPEC) effector NleE using proximity-enabled protein crosslinking. We show that ZPR1 assembles via liquid-liquid phase separation (LLPS) in vitro and regulates CHOP-mediated UPRER at the transcriptional level. Interestingly, in vitro studies show that the ZPR1 binding ability with K63-ubiquitin chains, which promotes LLPS of ZPR1, is disrupted by NleE. Further analyses indicate that EPEC restricts host UPRER pathways at the transcription level in a NleE-ZPR1 cascade-dependent manner. Together, our study reveals the mechanism by which EPEC interferes with CHOP-UPRER via regulating ZPR1 to help pathogens escape host defense. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Xiaoxiao Ouyang, Xueyun Wang, Pan Li, Qin Huang, Li Zhou, Jingxiang Li, Li Gao, Qi Sun, Fangni Chai, Shupan Guo, Zhihui Zhou, Xin Liu, Lunzhi Dai, Wei Cheng, Haiyan Ren. Bacterial effector restricts liquid-liquid phase separation of ZPR1 to antagonize host UPRER. Cell reports. 2023 Jul 25;42(7):112700