The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Dephosphorylation of the RNA Sensors RIG-I and MDA5 by the Phosphatase PP1 Is Essential for Innate Immune Signaling
Open accessAbstract
SUMMARY RIG-I and MDA5 have emerged as key cytosolic sensors for the detection of RNA viruses, leading to antiviral interferon (IFN) production. Recent studies highlighted the importance of posttranslational modification for controlling RIG-I antiviral activity. However, the regulation of MDA5 signal-transducing ability remains unclear. Here we show that MDA5 signaling activity is regulated by a dynamic balance between phosphorylation and dephosphorylation of its CARD domains. Employing a phosphatome RNAi screen, we identified PP1α and PP1γ as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation. Silencing of PP1α and PP1γ enhanced RIG-I and MDA5 CARD phosphorylation and reduced antiviral IFN-β production. PP1α and PP1γ depleted cells were impaired in their ability to induce interferon-stimulated gene expression, which resulted in enhanced RNA virus replication. This work identifies PP1α and PP1γ as regulators of antiviral innate immune responses to various RNA viruses, including influenza virus, paramyxovirus, dengue virus and picornavirus.
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Cites
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
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IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
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Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
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Immune Signaling by RIG-I-like Receptors
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VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling
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TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity
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Self-citationType I Inteferon Gene Induction by the Interferon Regulatory Factor Family of Transcription Factors
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Mass Spectrometry in Proteomics
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Mitochondria in innate immune signaling
Banoth, B., & Cassel, S. L. (2018) · Translational Research · doi:10.1016/j.trsl.2018.07.014 · Cited by 410
Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5
Brisse, M., & Ly, H. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01586 · Cited by 365
LINE1 contributes to autoimmunity through both RIG-I- and MDA5-mediated RNA sensing pathways
Zhao, K., Du, J., Peng, Y., Li, P., Wang, S., Wang, Y., Hou, J., Kang, J., Zheng, W., Hua, S., et al. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.02.007 · Cited by 106
Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids
Hu, M.-M., & Shu, H.-B. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062903 · Cited by 110
Metadata
- Authors
- Wies, E., Wang, M. K., Maharaj, N. P., Chen, K., Zhou, S., Finberg, R. W., & Gack, M. U.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 38
- Issue
- 3
- Pages
- 437-449
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2086138941
- Cited by
- 309
- References
- 34
- FWCI
- 14.47
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wies, E., Wang, M. K., Maharaj, N. P., Chen, K., Zhou, S., Finberg, R. W., & Gack, M. U. (2013). Dephosphorylation of the RNA Sensors RIG-I and MDA5 by the Phosphatase PP1 Is Essential for Innate Immune Signaling. Immunity. https://doi.org/10.1016/j.immuni.2012.11.018
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