The Ubiquitin E3 Ligase Parkin Inhibits Innate Antiviral Immunity Through K48-Linked Polyubiquitination of RIG-I and MDA5.
Innate immunity is the first-line defense against antiviral or antimicrobial infection. RIG-I and MDA5, which mediate the recognition of pathogen-derived nucleic acids, are essential for production of type I interferons (IFN). Here, we identified mitochondrion depolarization inducer carbonyl cyanide 3-chlorophenylhydrazone (CCCP) inhibited the response and antiviral activity of type I ... IFN during viral infection. Furthermore, we found that the PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin-protein ligase Parkin mediated mitophagy, thus negatively regulating the activation of RIG-I and MDA5. Parkin directly interacted with and catalyzed the K48-linked polyubiquitination and subsequent degradation of RIG-I and MDA5. Thus, we demonstrate that Parkin limits RLR-triggered innate immunity activation, suggesting Parkin as a potential therapeutic target for the control of viral infection.
Mesh Terms:
A549 Cells, Animals, Chlorocebus aethiops, DEAD Box Protein 58, HEK293 Cells, Host-Pathogen Interactions, Humans, Hydrazones, Immunity, Innate, Interferon Type I, Interferon-Induced Helicase, IFIH1, Mice, Mitochondria, Mitophagy, Protein Kinases, RAW 264.7 Cells, Receptors, Immunologic, Sendai virus, THP-1 Cells, Ubiquitin-Protein Ligases, Ubiquitination, Uncoupling Agents, Vero Cells, Vesiculovirus
A549 Cells, Animals, Chlorocebus aethiops, DEAD Box Protein 58, HEK293 Cells, Host-Pathogen Interactions, Humans, Hydrazones, Immunity, Innate, Interferon Type I, Interferon-Induced Helicase, IFIH1, Mice, Mitochondria, Mitophagy, Protein Kinases, RAW 264.7 Cells, Receptors, Immunologic, Sendai virus, THP-1 Cells, Ubiquitin-Protein Ligases, Ubiquitination, Uncoupling Agents, Vero Cells, Vesiculovirus
Front Immunol
Date: Sep. 29, 2020
PubMed ID: 32983119
View in: Pubmed Google Scholar
Download Curated Data For This Publication
230831
Switch View:
- Interactions 5