A ZBP1 isoform blocks ZBP1-mediated cell death
作者全名：Cai, Zhi-Yu; Wu, Puqi; Liang, Hao; Xie, Yu-Ze; Zhang, Bo-Xin; He, Cai-Ling; Yang, Cong-Rong; Li, Hongda; Mo, Wei; Yang, Zhang-Hua
作者地址：[Cai, Zhi-Yu; Wu, Puqi; Liang, Hao; Xie, Yu-Ze; He, Cai-Ling; Yang, Cong-Rong; Mo, Wei] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China; [Cai, Zhi-Yu; Zhang, Bo-Xin; Mo, Wei; Yang, Zhang-Hua] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Gastroenterol,Liangzhu Lab, Hangzhou 310012, Peoples R China; [Mo, Wei] Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Immunol, Hangzhou 310012, Peoples R China; [Li, Hongda; Mo, Wei] Chongqing Med Univ, Minist Educ, Inst Brain Sci & Dis, Key Lab Major Brain Dis & Aging Res, Chongqing 400016, Peoples R China
通信作者：Mo, W (通讯作者)，Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China.; Mo, W; Yang, ZH (通讯作者)，Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Gastroenterol,Liangzhu Lab, Hangzhou 310012, Peoples R China.; Mo, W (通讯作者)，Zhejiang Univ, Sch Med, Sch Basic Med Sci, Dept Immunol, Hangzhou 310012, Peoples R China.; Mo, W (通讯作者)，Chongqing Med Univ, Minist Educ, Inst Brain Sci & Dis, Key Lab Major Brain Dis & Aging Res, Chongqing 400016, Peoples R China.
来源：CELL REPORTS
ESI学科分类：MOLECULAR BIOLOGY & GENETICS
WOS号：WOS:001241290800001
JCR分区：Q1
影响因子：7.5
年份：2024
卷号：43
期号：5
开始页：
结束页：
文献类型：Article
关键词：
摘要：ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z -form NA (Z -NA) to promote cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here, we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppressor of the inflammatory signaling mediated by full-length ZBP1. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z -NA for Za domains of ZBP1. Cells from mice ( Ripk1 D325A/D325A ) with cleavage -resistant RIPK1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-dependent cell death. Intriguingly, Ripk1 D325A/D325A cells die spontaneously when ZBP1-S is deleted, indicating that cell death driven by ZBP1 is under the control of ZBP1-S. Thus, our findings reveal that alternative splicing of Zbp1 represents autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z -NA with ZBP1 could be an effective strategy against autoinflammations.
基金机构：National Natural Science Foundation of China [32225016, 32170751]; National Key R&D Pro- gram of China [2021YFA1101401]
基金资助正文：<BOLD>Acknowledgments</BOLD> The study was supported by the National Natural Science Foundation of China (32225016 to W.M. and 32170751 to Z.-H.Y.) and the National Key R&D Pro- gram of China (2021YFA1101401 to W.M.) .
