Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair-Reference-Cited by-同舟云学术

Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair

Published:2023-07-28 Issue:30 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Martinez Lagunas Kristel¹^ORCID,Savcigil Deniz Pinar¹^ORCID,Zrilic Matea¹^ORCID,Carvajal Fraile Carlos¹^ORCID,Craxton Andrew²^ORCID,Self Emily²^ORCID,Uranga-Murillo Iratxe³^ORCID,de Miguel Diego³^ORCID,Arias Maykel³⁴⁵,Willenborg Sebastian⁶^ORCID,Piekarek Michael⁶^ORCID,Albert Marie Christine⁷⁸,Nugraha Kalvin¹^ORCID,Lisewski Ina¹^ORCID,Janakova Erika¹^ORCID,Igual Natalia¹,Tonnus Wulf⁹¹⁰^ORCID,Hildebrandt Ximena¹⁷¹¹^ORCID,Ibrahim Mohammed¹⁷¹¹^ORCID,Ballegeer Marlies¹²¹³^ORCID,Saelens Xavier¹²¹³^ORCID,Kueh Andrew¹⁴¹⁵,Meier Pascal¹⁶^ORCID,Linkermann Andreas⁹¹⁰¹⁷^ORCID,Pardo Julian³⁴⁵^ORCID,Eming Sabine¹⁶⁷¹⁸^ORCID,Walczak Henning⁷⁸¹⁹^ORCID,MacFarlane Marion²^ORCID,Peltzer Nieves¹⁷¹¹^ORCID,Annibaldi Alessandro¹^ORCID

Affiliation:

1. Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch Strasse 21, 50931, Cologne, Germany.

2. MRC Toxicology Unit, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK.

3. Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Zaragoza, Spain.

4. Department of Microbiology, Radiology, Pediatry and Public Health, University of Zaragoza, Zaragoza, Spain.

5. CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.

6. Department of Dermatology, University of Cologne, 50937 Cologne, Germany.

7. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.

8. Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany.

9. Division of Nephrology, Department of Internal Medicine 3, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.

10. Biotechnology Center, Technische Universität Dresden, Dresden, Germany.

11. Department of Translational Genomics, University of Cologne, Weyertal 115b, 50931 Köln, Germany.

12. VIB-UGent Center for Medical Biotechnology, VIB, B-9052 Ghent, Belgium.

13. Department of Biochemistry and Microbiology, Ghent University, B-9000 Ghent, Belgium.

14. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

15. Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.

16. The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.

17. Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.

18. Institute of Zoology, Developmental Biology Unit, University of Cologne, 50674 Cologne, Germany.

19. Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College, London WC1E 6BT, UK.

Abstract

Cell death coordinates repair programs following pathogen attack and tissue injury. However, aberrant cell death can interfere with such programs and cause organ failure. Cellular FLICE-like inhibitory protein (cFLIP) is a crucial regulator of cell death and a substrate of Caspase-8. However, the physiological role of cFLIP cleavage by Caspase-8 remains elusive. Here, we found an essential role for cFLIP cleavage in restraining cell death in different pathophysiological scenarios. Mice expressing a cleavage-resistant cFLIP mutant, Cflip D377A , exhibited increased sensitivity to severe acute respiratory syndrome coronavirus (SARS-CoV)–induced lethality, impaired skin wound healing, and increased tissue damage caused by Sharpin deficiency. In vitro, abrogation of cFLIP cleavage sensitizes cells to tumor necrosis factor(TNF)–induced necroptosis and apoptosis by favoring complex-II formation. Mechanistically, the cell death–sensitizing effect of the D377A mutation depends on glutamine-469. These results reveal a crucial role for cFLIP cleavage in controlling the amplitude of cell death responses occurring upon tissue stress to ensure the execution of repair programs.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adg2829

Reference68 articles.

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