Intracellular interferon triggers Jak/Stat signaling cascade and induces p53-dependent antiviral protection
Intracellular interferons (IFNs) exert biological functions similar to those of extracellular IFNs, but the signal transduction pathway triggered by the intracellular ligands has not been fully revealed. We investigated the signaling cascade by sequence-specific knockdown of signaling molecules by m...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2005-04, Vol.329 (3), p.1139-1146 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Shin-Ya, Masaharu Hirai, Hideyo Satoh, Etsuko Kishida, Tsunao Asada, Hidetsugu Aoki, Fumiko Tsukamoto, Masako Imanishi, Jiro Mazda, Osam |
| description | Intracellular interferons (IFNs) exert biological functions similar to those of extracellular IFNs, but the signal transduction pathway triggered by the intracellular ligands has not been fully revealed. We investigated the signaling cascade by sequence-specific knockdown of signaling molecules by means of the RNA interference. Truncated IFN-β gene was constructed so that the N-terminal secretory signal sequence was deleted (SD.IFN-β). Cells transfected with this construct showed phosphorylation and activation of the STAT1 without any detectable secretion of the cytokine. The MHC class I expression was significantly augmented, while the augmentation was suppressed by short interfering RNA duplexes specific for JAK1, TYK2, and IFN-α/β receptor (IFNAR) 1 and 2c chains. The SD.IFN-β also induced p53 and phosphorylation of p53 at Ser
15. Specific silencing of p53 abrogated the antiviral effect of SD.IFN-β, suggesting that the tumor suppressor is critically involved in antiviral defense mediated by intracellular IFN. |
| doi_str_mv | 10.1016/j.bbrc.2005.02.088 |
| format | Article |
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15. Specific silencing of p53 abrogated the antiviral effect of SD.IFN-β, suggesting that the tumor suppressor is critically involved in antiviral defense mediated by intracellular IFN.</description><subject>Autocrine</subject><subject>Cell Line</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - virology</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Interferon</subject><subject>Interferon-beta - metabolism</subject><subject>Intracellular Fluid - metabolism</subject><subject>p53</subject><subject>Protein Methyltransferases - metabolism</subject><subject>Protein-Arginine N-Methyltransferases</subject><subject>RNA interference</subject><subject>Sarcoma, Ewing - metabolism</subject><subject>Sarcoma, Ewing - virology</subject><subject>Signal Transduction - physiology</subject><subject>STAT1</subject><subject>STAT1 Transcription Factor</subject><subject>Trans-Activators - metabolism</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Vesicular stomatitis Indiana virus - physiology</subject><subject>Virus Replication</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1r3DAQFaWl2Wz7B3ooPvVmZyRZlg29lJA2CQs5tIXehD7GizZeeSvJgf77aNmF3hLmMId5783Me4R8otBQoN3VrjEm2oYBiAZYA33_hqwoDFAzCu1bsgKArmYD_XNBLlPaAVDadsN7ckGFFExKtiKPdyFHbXGalknHyoeMccQ4hypHv91iTNW9frz6mXWukt8GPfmwraxOVjusdHCF4haLqToIXjs8YHAYcplk_-SjnqpDnDPa7Ofwgbwb9ZTw47mvye_vN7-ub-vNw4-762-b2raC5trogZoeuo6J1nEpDEfOuRjlOGpJe-3YaKQbxr4HoZFqlK1hRpaDJMieSr4mX066ZfXfBVNWe5-OL-qA85JUJ9uBDaJ9FUhlz3lXak3YCWjjnFLEUR2i3-v4T1FQxyzUTh2zUMcsFDBVsiikz2f1xezR_aeczS-ArycAFjOePEaVrMdg0flYHFNu9i_pPwO-EZxr</recordid><startdate>20050415</startdate><enddate>20050415</enddate><creator>Shin-Ya, Masaharu</creator><creator>Hirai, Hideyo</creator><creator>Satoh, Etsuko</creator><creator>Kishida, Tsunao</creator><creator>Asada, Hidetsugu</creator><creator>Aoki, Fumiko</creator><creator>Tsukamoto, Masako</creator><creator>Imanishi, Jiro</creator><creator>Mazda, Osam</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20050415</creationdate><title>Intracellular interferon triggers Jak/Stat signaling cascade and induces p53-dependent antiviral protection</title><author>Shin-Ya, Masaharu ; Hirai, Hideyo ; Satoh, Etsuko ; Kishida, Tsunao ; Asada, Hidetsugu ; Aoki, Fumiko ; Tsukamoto, Masako ; Imanishi, Jiro ; Mazda, Osam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-ba91b8066254d375b3e3335f7ffa718ad2fb7d9f8805ae1ae74b2b7cad7078173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Autocrine</topic><topic>Cell Line</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - virology</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Interferon</topic><topic>Interferon-beta - metabolism</topic><topic>Intracellular Fluid - metabolism</topic><topic>p53</topic><topic>Protein Methyltransferases - metabolism</topic><topic>Protein-Arginine N-Methyltransferases</topic><topic>RNA interference</topic><topic>Sarcoma, Ewing - metabolism</topic><topic>Sarcoma, Ewing - virology</topic><topic>Signal Transduction - physiology</topic><topic>STAT1</topic><topic>STAT1 Transcription Factor</topic><topic>Trans-Activators - metabolism</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Vesicular stomatitis Indiana virus - physiology</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shin-Ya, Masaharu</creatorcontrib><creatorcontrib>Hirai, Hideyo</creatorcontrib><creatorcontrib>Satoh, Etsuko</creatorcontrib><creatorcontrib>Kishida, Tsunao</creatorcontrib><creatorcontrib>Asada, Hidetsugu</creatorcontrib><creatorcontrib>Aoki, Fumiko</creatorcontrib><creatorcontrib>Tsukamoto, Masako</creatorcontrib><creatorcontrib>Imanishi, Jiro</creatorcontrib><creatorcontrib>Mazda, Osam</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shin-Ya, Masaharu</au><au>Hirai, Hideyo</au><au>Satoh, Etsuko</au><au>Kishida, Tsunao</au><au>Asada, Hidetsugu</au><au>Aoki, Fumiko</au><au>Tsukamoto, Masako</au><au>Imanishi, Jiro</au><au>Mazda, Osam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intracellular interferon triggers Jak/Stat signaling cascade and induces p53-dependent antiviral protection</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2005-04-15</date><risdate>2005</risdate><volume>329</volume><issue>3</issue><spage>1139</spage><epage>1146</epage><pages>1139-1146</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Intracellular interferons (IFNs) exert biological functions similar to those of extracellular IFNs, but the signal transduction pathway triggered by the intracellular ligands has not been fully revealed. We investigated the signaling cascade by sequence-specific knockdown of signaling molecules by means of the RNA interference. Truncated IFN-β gene was constructed so that the N-terminal secretory signal sequence was deleted (SD.IFN-β). Cells transfected with this construct showed phosphorylation and activation of the STAT1 without any detectable secretion of the cytokine. The MHC class I expression was significantly augmented, while the augmentation was suppressed by short interfering RNA duplexes specific for JAK1, TYK2, and IFN-α/β receptor (IFNAR) 1 and 2c chains. The SD.IFN-β also induced p53 and phosphorylation of p53 at Ser
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| subjects | Autocrine Cell Line DNA-Binding Proteins - metabolism Fibroblasts - metabolism Fibroblasts - virology Gene Silencing Humans Interferon Interferon-beta - metabolism Intracellular Fluid - metabolism p53 Protein Methyltransferases - metabolism Protein-Arginine N-Methyltransferases RNA interference Sarcoma, Ewing - metabolism Sarcoma, Ewing - virology Signal Transduction - physiology STAT1 STAT1 Transcription Factor Trans-Activators - metabolism Tumor Suppressor Protein p53 - metabolism Vesicular stomatitis Indiana virus - physiology Virus Replication |
| title | Intracellular interferon triggers Jak/Stat signaling cascade and induces p53-dependent antiviral protection |
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