Control of the inflammasome by the ubiquitin system

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Inflammation is the body’s response to danger. One of the first immune cell types to encounter danger is the macrophage. Macrophages sense danger signals such as extracellular ATP or bacterial toxins, derived from tissue damage or infection, and initiate the activation of an intracellular molecular complex called the inflammasome. The inflammasome consists of a cytosolic pattern recognition receptor, an adaptor molecule ASC (Apoptosis‐associated speck‐like protein containing a CARD), and the protease caspase‐1. Assembly of the complex leads to the cleavage and activation of caspase‐1 that triggers processing and release of the cytokines interleukin (IL)‐1β and IL‐18, and ultimately cell death via the process of pyroptosis. The ability to sense and respond to danger appropriately is critical for maintaining immune homeostasis. Dysregulation of inflammasomes contributes to the progression of chronic diseases prevalent in the aging population, such as Alzheimer’s disease, COPD and metabolic disease; hence, it is critical that activation of the inflammatory response and inflammasome activation are tightly regulated. Post‐translational modifications (PTMs) such as ubiquitination have recently emerged as important regulators of inflammasome assembly. However, the mechanisms by which PTMs regulate the inflammasome is still not understood. This review aims to summarize our knowledge to date on how the ubiquitin system controls inflammasome activation and where this area of research is heading.
    Original languageEnglish
    JournalThe FEBS Journal
    Early online date2 Nov 2019
    DOIs
    Publication statusPublished - 2019

    Keywords

    • Postranslational modifications
    • inflammsome
    • Ubiquitin
    • E3-enzymes
    • Deubiquitinases
    • inflammation
    • NLRP3
    • interleukin-1
    • caspase-1

    Research Beacons, Institutes and Platforms

    • Lydia Becker Institute

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