Institutional Repository of Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences
| Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis | |
| Jiang, Shuai1,2; Gu, Hanjie1,2,3; Zhao, Yan1,2,3; Sun, Li1,2 | |
| 2019-09-01 | |
| Source Publication | JOURNAL OF IMMUNOLOGY
 |
| ISSN | 0022-1767 |
| Volume | 203Issue:5Pages:1369-1382 |
| Corresponding Author | Sun, Li(lsun@qdio.ac.cn) |
| Abstract | Pyroptosis is a newly defined gasdermin (GSDM)-dependent inflammatory type of programmed cell death. Different from mammals, which have a panel of pyroptotic GSDM members (e.g., GSDMA-E), teleosts possess only GSDME. The pyroptotic activity and regulation mechanism of teleost GSDME remain to be elucidated. In this work, we investigated the activity of the teleost Cynoglossus semilaevis (tongue sole) GSDME (CsGSDME) in association with different caspases (CASPs). We found that CsGSDME exerted pyroptotic and bactericidal activities through its N-terminal domain. Unlike human GSDME, which is exclusively cleaved by CASP3, CsGSDME was cleaved by C. semilaevis CASP (CsCASP) 1 with high efficiency and by CsCASP3 and 7 with comparatively low efficiencies, and all cleavages occurred at the 243FEVD246 site in the interdomain linker region of CsGSDME. Mutation of Phe(243) to Asp/Ala and Asp(246) to Ala in 243FEVD246 altered the cleavage preference of CsCASP1, 3, and 7. Treatment with loss-of-function CsCASP mutants or inhibition of CsCASP activity resulted in failure of CsGSDME cleavage. CsCASP1-cleaved CsGSDME induced pyroptosis, whereas CsCASP3/7-cleaved CsGSDME and F243 mutants induced switching of cell death from apoptosis to pyroptosis. Analysis of 54 teleost GSDME sequences revealed a conserved tetrapeptide motif that fits well to the inherent cleavage site of CASP1. Taken together, the results of our study demonstrate a hitherto, to our knowledge, unrecognized GSDME cleavage mode in teleosts that is clearly different from that in mammals, thus providing an important insight into the activation mechanism of CASP-mediated, GSDM-executed pyroptosis in teleosts. |
| DOI | 10.4049/jimmunol.1900383 |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | National Natural Science Foundation of China[41876175] ; Shandong Major Science and Technology Innovation Project[2018SDKJ0302-2] ; National Key Research and Development Program of China[2018YFD0900504] ; Taishan Scholar Program of Shandong Province ; Distinguished Young Scientists Research Fund of the Key Laboratory of Experimental Marine Biology, Chinese Academy of Sciences[KLEMB-DYS03] |
| WOS Research Area | Immunology |
| WOS Subject | Immunology |
| WOS ID | WOS:000481646200027 |
| Publisher | AMER ASSOC IMMUNOLOGISTS |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.qdio.ac.cn/handle/337002/162382 |
| Collection | 实验海洋生物学重点实验室 |
| Corresponding Author | Sun, Li |
| Affiliation | 1.Chinese Acad Sci, Ctr Ocean Mega Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 2.Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao 266237, Shandong, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| First Author Affilication | Institute of Oceanology, Chinese Academy of Sciences |
| Corresponding Author Affilication | Institute of Oceanology, Chinese Academy of Sciences |
| Recommended Citation GB/T 7714 | Jiang, Shuai,Gu, Hanjie,Zhao, Yan,et al. Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis[J]. JOURNAL OF IMMUNOLOGY,2019,203(5):1369-1382. |
| APA | Jiang, Shuai,Gu, Hanjie,Zhao, Yan,&Sun, Li.(2019).Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis.JOURNAL OF IMMUNOLOGY,203(5),1369-1382. |
| MLA | Jiang, Shuai,et al."Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis".JOURNAL OF IMMUNOLOGY 203.5(2019):1369-1382. |
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