Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization
Previous studies revealed that phenylmethimazole (C10) inhibits IRF3 signaling, preventing dsRNA-induction of type 1 interferon gene expression, production, and downstream signaling. In the present study, we investigated the molecular basis for C10 inhibition of dsRNA-stimulated IRF3 signaling. IRF-...
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MDPI AG
2012-10-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/17/10/12365 |
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| author | Maria C. Courreges Noriko Kantake Douglas J. Goetz Frank L. Schwartz Kelly D. McCall |
| author_facet | Maria C. Courreges Noriko Kantake Douglas J. Goetz Frank L. Schwartz Kelly D. McCall |
| author_sort | Maria C. Courreges |
| collection | DOAJ |
| description | Previous studies revealed that phenylmethimazole (C10) inhibits IRF3 signaling, preventing dsRNA-induction of type 1 interferon gene expression, production, and downstream signaling. In the present study, we investigated the molecular basis for C10 inhibition of dsRNA-stimulated IRF3 signaling. IRF-3 Trans-AM assays were used to measure C10 effects on dsRNA induction of IRF3 DNA binding. Green fluorescent protein-labeled IRF3 was used to measure C10 effects on dsRNA-induced IRF3 nuclear translocation. Native PAGE, SDS PAGE, and western blotting were used to identify effects of C10 on IRF3 homodimer formation and phosphorylation, respectively. There was a significant impairment of dsRNA-induced IRF3 DNA binding activity in human embryonic kidney and pancreatic cancer cells with C10 treatment. C10 also blocked dsRNA-induced IRF3 nuclear translocation and homodimer formation without blocking serine 396 phosphorylation of IRF3. Together, these results indicate that C10 interferes with IRF3 signaling by blocking dsRNA-induced IRF3 homodimer formation, a prerequisite for nuclear translocation and DNA binding activities. |
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| format | Article |
| id | doaj.art-220fb7a660d54ccba67f4a67989d2e88 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T17:53:08Z |
| publishDate | 2012-10-01 |
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| series | Molecules |
| spelling | doaj.art-220fb7a660d54ccba67f4a67989d2e882022-12-22T01:39:00ZengMDPI AGMolecules1420-30492012-10-011710123651237710.3390/molecules171012365Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and HomodimerizationMaria C. CourregesNoriko KantakeDouglas J. GoetzFrank L. SchwartzKelly D. McCallPrevious studies revealed that phenylmethimazole (C10) inhibits IRF3 signaling, preventing dsRNA-induction of type 1 interferon gene expression, production, and downstream signaling. In the present study, we investigated the molecular basis for C10 inhibition of dsRNA-stimulated IRF3 signaling. IRF-3 Trans-AM assays were used to measure C10 effects on dsRNA induction of IRF3 DNA binding. Green fluorescent protein-labeled IRF3 was used to measure C10 effects on dsRNA-induced IRF3 nuclear translocation. Native PAGE, SDS PAGE, and western blotting were used to identify effects of C10 on IRF3 homodimer formation and phosphorylation, respectively. There was a significant impairment of dsRNA-induced IRF3 DNA binding activity in human embryonic kidney and pancreatic cancer cells with C10 treatment. C10 also blocked dsRNA-induced IRF3 nuclear translocation and homodimer formation without blocking serine 396 phosphorylation of IRF3. Together, these results indicate that C10 interferes with IRF3 signaling by blocking dsRNA-induced IRF3 homodimer formation, a prerequisite for nuclear translocation and DNA binding activities.http://www.mdpi.com/1420-3049/17/10/12365phenylmethimazole (C10)IRF3 |
| spellingShingle | Maria C. Courreges Noriko Kantake Douglas J. Goetz Frank L. Schwartz Kelly D. McCall Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization Molecules phenylmethimazole (C10) IRF3 |
| title | Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization |
| title_full | Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization |
| title_fullStr | Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization |
| title_full_unstemmed | Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization |
| title_short | Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization |
| title_sort | phenylmethimazole blocks dsrna induced irf3 nuclear translocation and homodimerization |
| topic | phenylmethimazole (C10) IRF3 |
| url | http://www.mdpi.com/1420-3049/17/10/12365 |
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