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| A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis | |
| 2022-05 | |
| 发表期刊 | NATURE CELL BIOLOGY (IF:17.3[JCR-2023],24.2[5-Year]) |
| ISSN | 1465-7392 |
| EISSN | 1476-4679 |
| 发表状态 | 已发表 |
| DOI | 10.1038/s41556-022-00894-z |
| 摘要 | ["Zhang et al. report that a non-canonical cGAS-STING pathway activates PERK-eIF2 alpha to elaborate cap-dependent mRNA translation and contributes to senescence and fibrosis.","Innate DNA sensing via the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) mechanism surveys microbial invasion and cellular damage and thus participates in various human infectious diseases, autoimmune diseases and cancers. However, how DNA sensing rapidly and adaptively shapes cellular physiology is incompletely known. Here we identify the STING-PKR-like endoplasmic reticulum kinase (PERK)-eIF2 alpha pathway, a previously unknown cGAS-STING mechanism, enabling an innate immunity control of cap-dependent messenger RNA translation. Upon cGAMP binding, STING at the ER binds and directly activates the ER-located kinase PERK via their intracellular domains, which precedes TBK1-IRF3 activation and is irrelevant to the unfolded protein response. The activated PERK phosphorylates eIF2 alpha, forming an inflammatory- and survival-preferred translation program. Notably, this STING-PERK-eIF2 alpha pathway is evolutionarily primitive and physiologically critical to cellular senescence and organ fibrosis. Pharmacologically or genetically targeting this non-canonical cGAS-STING pathway attenuated lung and kidney fibrosis. Collectively, the findings identify an alternative innate immune pathway and its critical role in organ fibrosis, report an innate immunity-directed translation program and suggest the therapeutic potential for targeting the STING-PERK pathway in treating fibrotic diseases."] |
| URL | 查看原文 |
| 收录类别 | SCI ; SCIE |
| 语种 | 英语 |
| 资助项目 | NSFC Projects[31830052,31725017] ; National Key Research and Development Program of China[2021YFA1301401] |
| WOS研究方向 | Cell Biology |
| WOS类目 | Cell Biology |
| WOS记录号 | WOS:000789719800002 |
| 出版者 | NATURE PORTFOLIO |
| 引用统计 | 正在获取...
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| 文献类型 | 期刊论文 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/180895 |
| 专题 | 生命科学与技术学院_PI研究组_席莹组 |
| 通讯作者 | Liang, Tingbo; Shen, Li; Xu, Pinglong |
| 作者单位 | 1.Zhejiang Univ, Life Sci Inst, MOE Key Lab Biosyst Homeostasis & Protect, Hangzhou, Peoples R China 2.Zhejiang Univ, Life Sci Inst, Zhejiang Prov Key Lab Canc Mol Cell Biol, Hangzhou, Peoples R China 3.Zhejiang Univ, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Sch Med, Hangzhou, Peoples R China 4.Zhejiang Univ, Affiliated Hosp 1, Zhejiang Prov Key Lab Pancreat Dis, Sch Med, Hangzhou, Peoples R China 5.Zhejiang Univ HIC ZJU, Hangzhou Global Sci & Technol Innovat Ctr, Hangzhou, Peoples R China 6.Zhejiang Univ, Canc Ctr, Hangzhou, Peoples R China 7.Fujian Normal Univ, Coll Life Sci, Biomed Res Ctr South China, Key Lab Innate Immune Biol Fujian Prov, Fuzhou, Peoples R China 8.Wenzhou Univ, Coll Life & Environm Sci, Zhejiang Prov Key Lab Water Environm & Marine Bio, Wenzhou, Peoples R China 9.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Dan,Liu, Yutong,Zhu, Yezhang,et al. A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis[J]. NATURE CELL BIOLOGY,2022. |
| APA | Zhang, Dan.,Liu, Yutong.,Zhu, Yezhang.,Zhang, Qian.,Guan, Hongxing.,...&Xu, Pinglong.(2022).A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis.NATURE CELL BIOLOGY. |
| MLA | Zhang, Dan,et al."A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis".NATURE CELL BIOLOGY (2022). |
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