Teleost Gasdermin E Is Cleaved by Caspase 1, 3, and 7 and Induces Pyroptosis

The Journal of Immunology : Official Journal of the American Association of Immunologists
Shuai JiangLi Sun

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 Phe243 to Asp/Ala and Asp246 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. ...Continue Reading

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Citations

Mar 1, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhuang WangDahai Yang
Dec 11, 2019·Cold Spring Harbor Perspectives in Biology·Kay Hofmann
Mar 3, 2020·Frontiers in Immunology·Eamy Nursaliza YaacobDaisy Vanrompay
Dec 6, 2020·Science Immunology·Zhibin Zhang, Judy Lieberman
Dec 6, 2020·Science Immunology·Shuai JiangLi Sun
Jan 8, 2021·International Journal of Molecular Sciences·Kohsuke Tsuchiya
Jul 6, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Qun WangGaofeng Zeng
Mar 28, 2021·Trends in Cell Biology·Elke De SchutterPeter Vandenabeele
May 1, 2021·International Journal of Molecular Sciences·Natsuki MorimotoJun-Ichi Hikima
May 5, 2021·Journal of Physiology and Biochemistry·Xue GouYunman Li
Jun 4, 2021·Journal of Inflammation Research·Abdullah Al MamunJian Xiao
Jul 13, 2021·Developmental and Comparative Immunology·Hao ChenDahai Yang
Aug 7, 2021·Journal of Molecular Biology·Christopher B RyderDerek W Abbott
Sep 17, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Abdullah Al MamunJian Xiao
Oct 3, 2021·Journal of Molecular Biology·Asen Daskalov, N Louise Glass

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