Science signaling, 2019-10, Vol.12 (601)
2019
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- Autor(en) / Beteiligte
- Titel
- LGP2 binds to PACT to regulate RIG-I- and MDA5-mediated antiviral responses
- Ist Teil von
- Science signaling, 2019-10, Vol.12 (601)
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) RIG-I, MDA5, and LGP2 stimulate inflammatory and antiviral responses by sensing nonself RNA molecules produced during viral replication. Here, we investigated how LGP2 regulates the RIG-I- and MDA5-dependent induction of type I interferon (IFN) signaling and showed that LGP2 interacted with different components of the RNA-silencing machinery. We identified a direct protein-protein interaction between LGP2 and the IFN-inducible, double-stranded RNA binding protein PACT. The LGP2-PACT interaction was mediated by the regulatory C-terminal domain of LGP2 and was necessary for inhibiting RIG-I-dependent responses and for amplifying MDA5-dependent responses. We described a point mutation within LGP2 that disrupted the LGP2-PACT interaction and led to the loss of LGP2-mediated regulation of RIG-I and MDA5 signaling. These results suggest a model in which the LGP2-PACT interaction regulates the inflammatory responses mediated by RIG-I and MDA5 and enables the cellular RNA-silencing machinery to coordinate with the innate immune response.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1945-0877eISSN: 1937-9145DOI: 10.1126/scisignal.aar3993Titel-ID: cdi_pubmed_primary_31575732
- Format
- –
- Schlagworte
- Animals, Antiviral Agents - metabolism, Chlorocebus aethiops, DEAD Box Protein 58 - genetics, DEAD Box Protein 58 - metabolism, Enterovirus B, Human - genetics, Enterovirus B, Human - physiology, HEK293 Cells, HeLa Cells, Humans, Interferon Type I - genetics, Interferon Type I - metabolism, Interferon-Induced Helicase, IFIH1 - genetics, Interferon-Induced Helicase, IFIH1 - metabolism, Mengovirus - genetics, Mengovirus - physiology, Protein Binding, Receptors, Immunologic, RNA Helicases - genetics, RNA Helicases - metabolism, RNA, Small Interfering - genetics, RNA, Small Interfering - metabolism, RNA, Viral - genetics, RNA, Viral - metabolism, RNA-Binding Proteins - genetics, RNA-Binding Proteins - metabolism, Signal Transduction - genetics, Vero Cells