Ubiquitin E3 ligase MID1 inhibits the innate immune response by ubiquitinating IRF3.
Immunology
; 163(3): 278-292, 2021 07.
Article
in En
| MEDLINE
| ID: mdl-33513265
ABSTRACT
Interferon regulatory factor 3 (IRF3) is a critical transcription factor for inducing production of type I interferons (IFN-I) and regulating host antiviral response. Although IRF3 activation during viral infection has been extensively studied, the inhibitory regulation of IRF3 remains largely unexplored. Here, we revealed that Midline-1 (MID1) is a ubiquitin E3 ligase of IRF3 that plays essential roles in regulating the production of IFN-I. We found that MID1 physically interacts with IRF3 and downregulates IRF3 protein levels. Next, we demonstrated that MID1 can induce K48-linked polyubiquitination of IRF3, thus lowing the protein stability of IRF3. Our further studies identified Lys313 as a major ubiquitin acceptor lysine of IRF3 induced by MID1. Finally, MID1-mediated ubiquitination and degradation of IRF3 restrict IFN-I production and cellular antiviral response. This study uncovers a role of MID1 in regulating innate antiviral immunity and may provide a potential target for enhancing host antiviral activity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Orthomyxoviridae Infections
/
Ubiquitin-Protein Ligases
/
Influenza, Human
/
Influenza A Virus, H1N1 Subtype
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Immunology
Year:
2021
Document type:
Article
Affiliation country:
China