ArticleThe EMBO journal2015
A non-canonical role of the p97 complex in RIG-I antiviral signaling.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
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- Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB.Molecular neurodegeneration · 2024Article
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- The response to influenza vaccination is associated with DNA methylation-driven regulation of T cell innate antiviral pathways.Clinical epigenetics · 2024Article
- The response to influenza vaccination is associated with DNA methylation-driven regulation of T cell innate antiviral pathways.Research square · 2024Article
- Longitudinal analysis of influenza vaccination implicates regulation of RIG-I signaling by DNA methylation.Scientific reports · 2024Article
- CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation.Cellular & molecular immunology · 2023Article
- The cryo-EM structure of the human ERAD retrotranslocation complex.Science advances · 2023Article
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- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- Role of CIV NS1 Protein in Innate Immunity and Viral Replication.International journal of molecular sciences · 2023Article
- Exploiting RIG-I-like receptor pathway for cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate.Cell & bioscience · 2022Article
- A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome.Frontiers in microbiology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RIG-I is a well-studied sensor of viral RNA that plays a key role in innate immunity. p97 regulates a variety of cellular events such as protein quality control, membrane reassembly, DNA repair, and the cell cycle. Here, we report a new role for p97 with Npl4-Ufd1 as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I. The p97 complex is able to directly bind both non-ubiquitinated RIG-I and the E3 ligase RNF125, promoting K48-linked ubiquitination of RIG-I at residue K181. Viral infection significantly strengthens the interaction between RIG-I and the p97 complex by a conformational change of RIG-I that exposes the CARDs and through K63-linked ubiquitination of these CARDs. Disruption of the p97 complex enhances RIG-I antiviral signaling. Consistently, administration of compounds targeting p97 ATPase activity was shown to inhibit viral replication and protect mice from vesicular stomatitis virus (VSV) infection. Overall, our study uncovered a previously unrecognized role for the p97 complex in protein ubiquitination and revealed the p97 complex as a potential drug target in antiviral therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.