Linear ubiquitination induces NEMO phase separation to activate NF-κB signaling.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
15
07
2022
revised:
09
01
2023
accepted:
09
01
2023
entrez:
31
1
2023
pubmed:
1
2
2023
medline:
3
2
2023
Statut:
epublish
Résumé
The NF-κB essential modulator NEMO is the core regulatory component of the inhibitor of κB kinase complex, which is a critical checkpoint in canonical NF-κB signaling downstream of innate and adaptive immune receptors. In response to various stimuli, such as TNF or IL-1β, NEMO binds to linear or M1-linked ubiquitin chains generated by LUBAC, promoting its oligomerization and subsequent activation of the associated kinases. Here we show that M1-ubiquitin chains induce phase separation of NEMO and the formation of NEMO assemblies in cells after exposure to IL-1β. Phase separation is promoted by both binding of NEMO to linear ubiquitin chains and covalent linkage of M1-ubiquitin to NEMO and is essential but not sufficient for its phase separation. Supporting the functional relevance of NEMO phase separation in signaling, a pathogenic NEMO mutant, which is impaired in both binding and linkage to linear ubiquitin chains, does not undergo phase separation and is defective in mediating IL-1β-induced NF-κB activation.
Identifiants
pubmed: 36720498
pii: 6/4/e202201607
doi: 10.26508/lsa.202201607
pmc: PMC9889916
pii:
doi:
Substances chimiques
NF-kappa B
0
I-kappa B Kinase
EC 2.7.11.10
Ubiquitin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Goel et al.
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