Immunity (Cambridge, Mass.), 2009-03, Vol.30 (3), p.397-407
2009
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- Autor(en) / Beteiligte
- Titel
- The Ubiquitin Ligase RNF5 Regulates Antiviral Responses by Mediating Degradation of the Adaptor Protein MITA
- Ist Teil von
- Immunity (Cambridge, Mass.), 2009-03, Vol.30 (3), p.397-407
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2009
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Viral infection activates transcription factors NF-κB and IRF3, which collaborate to induce type I interferons (IFNs) and elicit innate antiviral response. MITA (also known as STING) has recently been identified as an adaptor that links virus-sensing receptors to IRF3 activation. Here, we showed that the E3 ubiquitin ligase RNF5 interacted with MITA in a viral-infection-dependent manner. Overexpression of RNF5 inhibited virus-triggered IRF3 activation, IFNB1 expression, and cellular antiviral response, whereas knockdown of RNF5 had opposite effects. RNF5 targeted MITA at Lys150 for ubiquitination and degradation after viral infection. Both MITA and RNF5 were located at the mitochondria and endoplasmic reticulum (ER) and viral infection caused their redistribution to the ER and mitochondria, respectively. We further found that virus-induced ubiquitination and degradation of MITA by RNF5 occurred at the mitochondria. These findings suggest that RNF5 negatively regulates virus-triggered signaling by targeting MITA for ubiquitination and degradation at the mitochondria.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2009.01.008Titel-ID: cdi_proquest_miscellaneous_67051111
- Format
- –
- Schlagworte
- Adaptor Proteins, Vesicular Transport - metabolism, Animals, CELLIMMUNO, Cells, Cultured, Cloning, DNA-Binding Proteins - genetics, DNA-Binding Proteins - immunology, Experiments, Gene Expression Regulation, Gene Knockdown Techniques, HeLa Cells, Humans, Immune system, Interferon-beta - genetics, Interferon-beta - metabolism, Interferon-Stimulated Gene Factor 3, gamma Subunit - genetics, Interferon-Stimulated Gene Factor 3, gamma Subunit - metabolism, Kinases, Membrane Proteins - metabolism, Mice, Mitochondria, MOLIMMUNO, NF-kappa B - genetics, NF-kappa B - metabolism, Promoter Regions, Genetic, Proteins, Signal Transduction, Studies, Transcription factors, Ubiquitin-Protein Ligases, Up-Regulation, Viral infections, Virus Diseases - immunology, Viruses - immunology