The Ubiquitin Ligase RNF5 Regulates Antiviral Responses by Mediating Degradation of the Adaptor Protein MITA
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 tha...
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| Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2009-03, Vol.30 (3), p.397-407 |
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| creator | Zhong, Bo Zhang, Lu Lei, Caoqi Li, Ying Mao, Ai-Ping Yang, Yan Wang, Yan-Yi Zhang, Xiao-Lian Shu, Hong-Bing |
| description | 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. |
| doi_str_mv | 10.1016/j.immuni.2009.01.008 |
| format | Article |
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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.</description><identifier>ISSN: 1074-7613</identifier><identifier>EISSN: 1097-4180</identifier><identifier>DOI: 10.1016/j.immuni.2009.01.008</identifier><identifier>PMID: 19285439</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Immunity (Cambridge, Mass.), 2009-03, Vol.30 (3), p.397-407</ispartof><rights>2009 Elsevier Inc.</rights><rights>Copyright Elsevier Limited Mar 20, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c531t-5b4e9ab73c0d9610f713a23c8f7972c54f5bb4f0c2884c89a1afe17a1034621e3</citedby><cites>FETCH-LOGICAL-c531t-5b4e9ab73c0d9610f713a23c8f7972c54f5bb4f0c2884c89a1afe17a1034621e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.immuni.2009.01.008$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19285439$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhong, Bo</creatorcontrib><creatorcontrib>Zhang, Lu</creatorcontrib><creatorcontrib>Lei, Caoqi</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><creatorcontrib>Mao, Ai-Ping</creatorcontrib><creatorcontrib>Yang, Yan</creatorcontrib><creatorcontrib>Wang, Yan-Yi</creatorcontrib><creatorcontrib>Zhang, Xiao-Lian</creatorcontrib><creatorcontrib>Shu, Hong-Bing</creatorcontrib><title>The Ubiquitin Ligase RNF5 Regulates Antiviral Responses by Mediating Degradation of the Adaptor Protein MITA</title><title>Immunity (Cambridge, Mass.)</title><addtitle>Immunity</addtitle><description>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.</description><subject>Adaptor Proteins, Vesicular Transport - metabolism</subject><subject>Animals</subject><subject>CELLIMMUNO</subject><subject>Cells, Cultured</subject><subject>Cloning</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - immunology</subject><subject>Experiments</subject><subject>Gene Expression Regulation</subject><subject>Gene Knockdown Techniques</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Immune system</subject><subject>Interferon-beta - genetics</subject><subject>Interferon-beta - metabolism</subject><subject>Interferon-Stimulated Gene Factor 3, gamma Subunit - genetics</subject><subject>Interferon-Stimulated Gene Factor 3, gamma Subunit - metabolism</subject><subject>Kinases</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mitochondria</subject><subject>MOLIMMUNO</subject><subject>NF-kappa B - genetics</subject><subject>NF-kappa B - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Signal Transduction</subject><subject>Studies</subject><subject>Transcription factors</subject><subject>Ubiquitin-Protein Ligases</subject><subject>Up-Regulation</subject><subject>Viral infections</subject><subject>Virus Diseases - immunology</subject><subject>Viruses - immunology</subject><issn>1074-7613</issn><issn>1097-4180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV-L1DAUxYMo7h_9BiIBwbfWe9u0aV6EYXXXhVmVZfY5pOntmKFtZpN2Yb-9GWZA8EGTh1wuv3MuuYexdwg5Atafdrkbx2VyeQGgcsAcoHnBzhGUzAQ28PJQS5HJGsszdhHjDgBFpeA1O0NVNJUo1TkbNr-IP7TucXGzm_jabU0kfv_9uuL3tF0GM1Pkq2l2Ty6YIfXi3k8x9dpnfkedM0m15V9oG0yXaj9x3_M5ea46s5994D-Dnyk5391uVm_Yq94Mkd6e3kv2cP11c_UtW_-4ub1arTNblThnVStImVaWFjpVI_QSS1OUtumlkoWtRF-1rejBFk0jbKMMmp5QGoRS1AVSeck-Hn33wT8uFGc9umhpGMxEfom6llBhOv8FCxBSoBIJ_PAXuPNLmNInNFYgilqkmyhxpGzwMQbq9T640YRnjaAPoemdPoamD6FpQJ1CS7L3J_OlHan7IzqllIDPR4DS0p4cBR2to8mm_Qeys-68-_eE3198qLo</recordid><startdate>20090320</startdate><enddate>20090320</enddate><creator>Zhong, Bo</creator><creator>Zhang, Lu</creator><creator>Lei, Caoqi</creator><creator>Li, Ying</creator><creator>Mao, Ai-Ping</creator><creator>Yang, Yan</creator><creator>Wang, Yan-Yi</creator><creator>Zhang, Xiao-Lian</creator><creator>Shu, Hong-Bing</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20090320</creationdate><title>The Ubiquitin Ligase RNF5 Regulates Antiviral Responses by Mediating Degradation of the Adaptor Protein MITA</title><author>Zhong, Bo ; Zhang, Lu ; Lei, Caoqi ; Li, Ying ; Mao, Ai-Ping ; Yang, Yan ; Wang, Yan-Yi ; Zhang, Xiao-Lian ; Shu, Hong-Bing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c531t-5b4e9ab73c0d9610f713a23c8f7972c54f5bb4f0c2884c89a1afe17a1034621e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adaptor Proteins, Vesicular Transport - metabolism</topic><topic>Animals</topic><topic>CELLIMMUNO</topic><topic>Cells, Cultured</topic><topic>Cloning</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - immunology</topic><topic>Experiments</topic><topic>Gene Expression Regulation</topic><topic>Gene Knockdown Techniques</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Immune system</topic><topic>Interferon-beta - genetics</topic><topic>Interferon-beta - metabolism</topic><topic>Interferon-Stimulated Gene Factor 3, gamma Subunit - genetics</topic><topic>Interferon-Stimulated Gene Factor 3, gamma Subunit - metabolism</topic><topic>Kinases</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Mitochondria</topic><topic>MOLIMMUNO</topic><topic>NF-kappa B - genetics</topic><topic>NF-kappa B - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>Signal Transduction</topic><topic>Studies</topic><topic>Transcription factors</topic><topic>Ubiquitin-Protein Ligases</topic><topic>Up-Regulation</topic><topic>Viral infections</topic><topic>Virus Diseases - immunology</topic><topic>Viruses - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhong, Bo</creatorcontrib><creatorcontrib>Zhang, Lu</creatorcontrib><creatorcontrib>Lei, Caoqi</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><creatorcontrib>Mao, Ai-Ping</creatorcontrib><creatorcontrib>Yang, Yan</creatorcontrib><creatorcontrib>Wang, Yan-Yi</creatorcontrib><creatorcontrib>Zhang, Xiao-Lian</creatorcontrib><creatorcontrib>Shu, Hong-Bing</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Immunity (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhong, Bo</au><au>Zhang, Lu</au><au>Lei, Caoqi</au><au>Li, Ying</au><au>Mao, Ai-Ping</au><au>Yang, Yan</au><au>Wang, Yan-Yi</au><au>Zhang, Xiao-Lian</au><au>Shu, Hong-Bing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Ubiquitin Ligase RNF5 Regulates Antiviral Responses by Mediating Degradation of the Adaptor Protein MITA</atitle><jtitle>Immunity (Cambridge, Mass.)</jtitle><addtitle>Immunity</addtitle><date>2009-03-20</date><risdate>2009</risdate><volume>30</volume><issue>3</issue><spage>397</spage><epage>407</epage><pages>397-407</pages><issn>1074-7613</issn><eissn>1097-4180</eissn><abstract>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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19285439</pmid><doi>10.1016/j.immuni.2009.01.008</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 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 |
| title | The Ubiquitin Ligase RNF5 Regulates Antiviral Responses by Mediating Degradation of the Adaptor Protein MITA |
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