Pathogen blockade of TAK1 triggers caspase-8–dependent cleavage of gasdermin D and cell death-Reference-Cited by-同舟云学术

Pathogen blockade of TAK1 triggers caspase-8–dependent cleavage of gasdermin D and cell death

Published:2018-10-25 Issue:6418 Volume:362 Page:1064-1069
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Orning Pontus¹²^ORCID,Weng Dan¹³,Starheim Kristian¹²,Ratner Dmitry¹^ORCID,Best Zachary¹^ORCID,Lee Bettina⁴,Brooks Alexandria¹^ORCID,Xia Shiyu⁵,Wu Hao⁵^ORCID,Kelliher Michelle A.⁶^ORCID,Berger Scott B.⁷,Gough Peter J.⁷^ORCID,Bertin John⁷,Proulx Megan M.⁸^ORCID,Goguen Jon D.⁸,Kayagaki Nobuhiko⁴,Fitzgerald Katherine A.¹²,Lien Egil¹²^ORCID

Affiliation:

1. Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

2. Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway.

3. Center for Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China.

4. Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA.

5. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115, USA.

6. Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

7. Pattern Recognition Receptor Discovery Performance Unit, Immuno-inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426, USA.

8. Department of Microbiology and Physiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Abstract

Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IκB kinase (IKK) by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8–dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome–dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.

Funder

National Institutes of Health

National Institute of Allergy and Infectious Diseases

The Research Council of Norway

The Norwegian Cancer Society

Norwegian Cancer Society

UMass Medical School Summer Undergraduate Research Program

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference57 articles.