IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v471y2011i7338d10.1038_nature09852.html
   My bibliography  Save this article

Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis

Author

Listed:
  • Andrew Oberst

    (Dept. of Immunology, St. Jude Children’s Research Hospital)

  • Christopher P. Dillon

    (Dept. of Immunology, St. Jude Children’s Research Hospital)

  • Ricardo Weinlich

    (Dept. of Immunology, St. Jude Children’s Research Hospital)

  • Laura L. McCormick

    (Dept. of Immunology, St. Jude Children’s Research Hospital)

  • Patrick Fitzgerald

    (Dept. of Immunology, St. Jude Children’s Research Hospital)

  • Cristina Pop

    (Program in Apoptosis and Cell Death Research, Sanford-Burnham Medical Research Institute)

  • Razq Hakem

    (Ontario Cancer Institute, University of Toronto)

  • Guy S. Salvesen

    (Program in Apoptosis and Cell Death Research, Sanford-Burnham Medical Research Institute)

  • Douglas R. Green

    (Dept. of Immunology, St. Jude Children’s Research Hospital)

Abstract

Caspase-8 joins RIPK at the death Caspase-8 mediates apoptosis induced by 'death receptors' on the cell's surface. At the same time, it is able to prevent receptor interacting protein kinase (RIPK)-dependent necrosis. Without caspase-8, mice die during embryonic development, but why this happens is not clear. Two groups show that this lethality is not caused by the absence of apoptosis, but by the RIPK3-dependent necrosis that is unleashed without caspase-8. Mice lacking both caspase-8 and RIP3 develop into viable, immunocompetent adults, but have a progressive lymphoaccumulative disease similar to that in mice that lack the CD95 death receptor. Oberst et al. also show that caspase-8 forms a proteolytically active complex with FLICE-like inhibitory protein long (FLIPL), and that this complex is required for protection against RIP3-dependent necrosis.

Suggested Citation

  • Andrew Oberst & Christopher P. Dillon & Ricardo Weinlich & Laura L. McCormick & Patrick Fitzgerald & Cristina Pop & Razq Hakem & Guy S. Salvesen & Douglas R. Green, 2011. "Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis," Nature, Nature, vol. 471(7338), pages 363-367, March.
    • Handle: RePEc:nat:nature:v:471:y:2011:i:7338:d:10.1038_nature09852
    DOI: 10.1038/nature09852
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature09852
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature09852?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Maria C. Tanzer & Isabell Bludau & Che A. Stafford & Veit Hornung & Matthias Mann, 2021. "Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Joo-Hui Han & Rajendra Karki & R. K. Subbarao Malireddi & Raghvendra Mall & Roman Sarkar & Bhesh Raj Sharma & Jonathon Klein & Harmut Berns & Harshan Pisharath & Shondra M. Pruett-Miller & Sung-Jin Ba, 2024. "NINJ1 mediates inflammatory cell death, PANoptosis, and lethality during infection conditions and heat stress," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Chao-Yu Yang & Chia-I Lien & Yi-Chun Tseng & Yi-Fan Tu & Arkadiusz W. Kulczyk & Yen-Chen Lu & Yin-Ting Wang & Tsung-Wei Su & Li-Chung Hsu & Yu-Chih Lo & Su-Chang Lin, 2024. "Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Chao-Yu Yang & Yi-Chun Tseng & Yi-Fan Tu & Bai-Jiun Kuo & Li-Chung Hsu & Chia-I Lien & You-Sheng Lin & Yin-Ting Wang & Yen-Chen Lu & Tsung-Wei Su & Yu-Chih Lo & Su-Chang Lin, 2024. "Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Esther Hoste & Kim Lecomte & Karl Annusver & Niels Vandamme & Jana Roels & Sophia Maschalidi & Lien Verboom & Hanna-Kaisa Vikkula & Mozes Sze & Lisette Van Hove & Kevin Verstaen & Arne Martens & Tino , 2021. "OTULIN maintains skin homeostasis by controlling keratinocyte death and stem cell identity," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:471:y:2011:i:7338:d:10.1038_nature09852. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.