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REUL Is a Novel E3 Ubiquitin Ligase and Stimulator of Retinoic-Acid-Inducible Gene-I
- Source :
- PLoS ONE, PLoS ONE, Vol 4, Iss 6, p e5760 (2009)
- Publication Year :
- 2009
- Publisher :
- Public Library of Science, 2009.
-
Abstract
- RIG-I and MDA5 are cytoplasmic sensors that recognize different species of viral RNAs, leads to activation of the transcription factors IRF3 and NF-kappaB, which collaborate to induce type I interferons. In this study, we identified REUL, a RING-finger protein, as a specific RIG-I-interacting protein. REUL was associated with RIG-I, but not MDA5, through its PRY and SPRY domains. Overexpression of REUL potently potentiated RIG-I-, but not MDA5-mediated downstream signalling and antiviral activity. In contrast, the RING domain deletion mutant of REUL suppressed Sendai virus (SV)-induced, but not cytoplasmic polyI:C-induced activation of IFN-beta promoter. Knockdown of endogenous REUL by RNAi inhibited SV-triggered IFN-beta expression, and also increased VSV replication. Full-length RIG-I, but not the CARD domain deletion mutant of RIG-I, underwent ubiquitination induced by REUL. The Lys 154, 164, and 172 residues of the RIG-I CARD domain were critical for efficient REUL-mediated ubiquitination, as well as the ability of RIG-I to induce activation of IFN-beta promoter. These findings suggest that REUL is an E3 ubiquitin ligase of RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity.
- Subjects :
- TRIM25
Cytoplasm
viruses
Ubiquitin-Protein Ligases
Immunology/Innate Immunity
Molecular Sequence Data
lcsh:Medicine
chemical and pharmacologic phenomena
Antiviral Agents
Models, Biological
Sendai virus
Cell Biology/Cell Signaling
DEAD-box RNA Helicases
Ubiquitin
RNA interference
Immunology/Immunity to Infections
Humans
Amino Acid Sequence
Receptors, Immunologic
lcsh:Science
Promoter Regions, Genetic
Transcription factor
Multidisciplinary
biology
Sequence Homology, Amino Acid
lcsh:R
virus diseases
MDA5
Interferon-beta
biochemical phenomena, metabolism, and nutrition
biology.organism_classification
Molecular biology
Ubiquitin ligase
Protein Structure, Tertiary
CARD domain
biology.protein
DEAD Box Protein 58
lcsh:Q
RNA Interference
biological phenomena, cell phenomena, and immunity
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....0bad7cd9ec3931635bccac84c31c29b9