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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
Corresponding AuthorSun, Li(
AbstractPyroptosis 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.
Indexed BySCI
Funding ProjectNational 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 AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000481646200027
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Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Corresponding AuthorSun, Li
Affiliation1.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 AffilicationInstitute of Oceanology, Chinese Academy of Sciences
Corresponding Author AffilicationInstitute 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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