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Updated: Jun 30, 2026
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Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Linear ubiquitin chain assembly complex contributes to NLRP3-mediated pyroptotic cell death
Tiphaine Douanne1,2, Rosalie Moreau1,2, Valeria Trapani1,2
1Team SOAP, CRCINA, INSERM, CNRS, Université de Nantes, Nantes, France.
Iscience
|June 29, 2026
Summary
Linear ubiquitination regulates pyroptosis, a inflammatory cell death. This process, involving the LUBAC complex and OTULIN, is crucial for both priming and execution phases, independently of NLRP3.
Area of Science:
- Cellular Biology
- Immunology
- Biochemistry
Background:
- Pyroptosis is a highly inflammatory programmed cell death pathway regulated by a two-step process: priming and execution.
- Linear (Met1-linked) ubiquitination, mediated by the LUBAC complex, is implicated in pyroptosis, but its precise role remains unclear.
Purpose of the Study:
- To elucidate the mechanisms by which linear ubiquitination regulates pyroptosis.
- To determine the role of linear ubiquitination in the priming and execution phases of pyroptosis.
Main Methods:
- Genetic deletion of LUBAC enzymes and the deubiquitinase OTULIN.
- Pharmacological inhibition of LUBAC.
- Optogenetic modeling to bypass the priming phase of pyroptosis.
Main Results:
- Met1-linked ubiquitin chains assemble during both priming and execution phases of pyroptosis, independent of NLRP3.
- Genetic deletion or pharmacological inhibition of LUBAC impairs pyroptosis.
- Absence of OTULIN enhances pyroptosis, while its inhibition suggests a role in pyroptosis execution.
Conclusions:
- Linear ubiquitination is a critical regulator of pyroptosis, acting in both priming and execution phases.
- The LUBAC complex and OTULIN are key players in controlling pyroptosis via linear ubiquitination.
- Met1-linked ubiquitination is essential for the execution phase of pyroptosis.
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