LUBAC-mediated linear ubiquitination: a crucial regulator of immune signaling
Open accessAbstract
Ubiquitination is a reversible post-translational modification in which ubiquitin chains are conjugated to target proteins to modulate protein function. The type of ubiquitin chain determines the mode of protein regulation. It has been shown that ubiquitin chains are formed via one of seven Lys residues in ubiquitin, and several types of ubiquitin chains are found in cells. We identified a new type of linear ubiquitin chain linked through the N-terminal Met of ubiquitin and assembled by the linear ubiquitin chain assembly complex (LUBAC), which is specific for linear chains. The discovery of linear ubiquitin chains and LUBAC is considered as a paradigm shift in ubiquitin research because linear ubiquitination is exclusive to animals, despite the existence of ubiquitination throughout eukaryotic kingdoms. Linear ubiquitination plays a critical role in immune signaling and cell death regulation. Dysregulation of LUBAC-mediated linear ubiquitination underlies various human diseases, including autoinflammation, autoimmunity, infection, and malignant tumors. This review summarizes the current status of linear ubiquitination research.
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The LUBAC is reportedly essential for NLRP3 inflammasome activation and acts as a key innate immune regulator.
“For instance, the LUBAC is reportedly essential for NLRP3 inflammasome activation27 and thus acts as a key innate immune regulator28.”
From New insights into the genetic etiology of Alzheimer’s disease and related dementias (2022) · cites this paper as [28]
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- Authors
- IWAI, K.
- Affiliations
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University
- Venue
- Proceedings of the Japan Academy, Series B
- Publisher
- Japan Academy
- Published
- 2021-03-11
- Volume
- 97
- Issue
- 3
- Pages
- 120-133
- ISSN
- 0386-2208 (ISSN-L)
- 1349-2896
- PMC
- PMC8019854
- OpenAlex
- W3134540309
- Cited by
- 37
- References
- 99
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 5 · 2021: 4
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Proceedings of the Japan Academy Series B (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (18H05499, 17H06174)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- linear ubiquitination, LUBAC, linear ubiquitin chains, ubiquitin chains, immune signaling, cell death regulation, autoinflammation, autoimmunity, infection, cancer, post-translational modification
- MeSH terms
- Animals, Humans, Signal Transduction, Ubiquitin, Ubiquitination
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