Cited by 37Ubiquitin and proteasome pathwaysNF-κB Signaling PathwaysImmune Response and Inflammation

LUBAC-mediated linear ubiquitination: a crucial regulator of immune signaling

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IWAI, Kazuhiro·2021·Proceedings of the Japan Academy, Series B

Abstract

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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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
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
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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