E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells
Upon recognition of dsRNA, toll-like receptor 3 (TLR3) recruits the adaptor protein TRIF to activate IRF3 and NF-κB signaling, initiating innate immune responses. The ubiquitination of TLR3 downstream signaling molecules and their roles in the innate response have been discovered; however, whether T...
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| Veröffentlicht in: | Cellular & molecular immunology 2020-08, Vol.17 (8), p.865-874 |
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| creator | Song, Xiaoqi Liu, Shuo Wang, Wendie Ma, Zhongfei Cao, Xuetao Jiang, Minghong |
| description | Upon recognition of dsRNA, toll-like receptor 3 (TLR3) recruits the adaptor protein TRIF to activate IRF3 and NF-κB signaling, initiating innate immune responses. The ubiquitination of TLR3 downstream signaling molecules and their roles in the innate response have been discovered; however, whether TLR3 itself is ubiquitinated and then functionally involved remains to be elucidated. By immunoprecipitating TLR3-binding proteins in macrophages, we identified ring finger protein 170 (RNF170) as a TLR3-binding E3 ligase. RNF170 mediated the K48-linked polyubiquitination of K766 in the TIR domain of TLR3 and promoted the degradation of TLR3 through the proteasome pathway. The genetic ablation of RNF170 selectively augmented TLR3-triggered innate immune responses both in vitro and in vivo. Our results reveal a novel role for RNF170 in selectively inhibiting TLR3-triggered innate immune responses by promoting TLR3 degradation. |
| doi_str_mv | 10.1038/s41423-019-0236-y |
| format | Article |
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The ubiquitination of TLR3 downstream signaling molecules and their roles in the innate response have been discovered; however, whether TLR3 itself is ubiquitinated and then functionally involved remains to be elucidated. By immunoprecipitating TLR3-binding proteins in macrophages, we identified ring finger protein 170 (RNF170) as a TLR3-binding E3 ligase. RNF170 mediated the K48-linked polyubiquitination of K766 in the TIR domain of TLR3 and promoted the degradation of TLR3 through the proteasome pathway. The genetic ablation of RNF170 selectively augmented TLR3-triggered innate immune responses both in vitro and in vivo. Our results reveal a novel role for RNF170 in selectively inhibiting TLR3-triggered innate immune responses by promoting TLR3 degradation.</description><identifier>ISSN: 1672-7681</identifier><identifier>EISSN: 2042-0226</identifier><identifier>DOI: 10.1038/s41423-019-0236-y</identifier><identifier>PMID: 31076723</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/262/2106/2108 ; 631/80/304 ; 631/80/86/2364 ; Antibodies ; Aquatic life ; Biomedical and Life Sciences ; Biomedicine ; Double-stranded RNA ; Immune response ; Immunology ; Innate immunity ; Interferon regulatory factor 3 ; Macrophages ; Medical Microbiology ; Microbiology ; NF-κB protein ; Phosphates ; Proteasomes ; TLR3 protein ; Toll-like receptors ; Ubiquitin ; Ubiquitin-protein ligase ; Ubiquitination ; Vaccine</subject><ispartof>Cellular & molecular immunology, 2020-08, Vol.17 (8), p.865-874</ispartof><rights>CSI and USTC 2019</rights><rights>CSI and USTC 2019.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-918ffc908f6be0d90525cbc744bc7a78ea0f7b54f18239e682d14f17e9faac513</citedby><cites>FETCH-LOGICAL-c470t-918ffc908f6be0d90525cbc744bc7a78ea0f7b54f18239e682d14f17e9faac513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395739/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395739/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31076723$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Xiaoqi</creatorcontrib><creatorcontrib>Liu, Shuo</creatorcontrib><creatorcontrib>Wang, Wendie</creatorcontrib><creatorcontrib>Ma, Zhongfei</creatorcontrib><creatorcontrib>Cao, Xuetao</creatorcontrib><creatorcontrib>Jiang, Minghong</creatorcontrib><title>E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells</title><title>Cellular & molecular immunology</title><addtitle>Cell Mol Immunol</addtitle><addtitle>Cell Mol Immunol</addtitle><description>Upon recognition of dsRNA, toll-like receptor 3 (TLR3) recruits the adaptor protein TRIF to activate IRF3 and NF-κB signaling, initiating innate immune responses. 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Our results reveal a novel role for RNF170 in selectively inhibiting TLR3-triggered innate immune responses by promoting TLR3 degradation.</description><subject>631/250/262/2106/2108</subject><subject>631/80/304</subject><subject>631/80/86/2364</subject><subject>Antibodies</subject><subject>Aquatic life</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Double-stranded RNA</subject><subject>Immune response</subject><subject>Immunology</subject><subject>Innate immunity</subject><subject>Interferon regulatory factor 3</subject><subject>Macrophages</subject><subject>Medical Microbiology</subject><subject>Microbiology</subject><subject>NF-κB protein</subject><subject>Phosphates</subject><subject>Proteasomes</subject><subject>TLR3 protein</subject><subject>Toll-like receptors</subject><subject>Ubiquitin</subject><subject>Ubiquitin-protein ligase</subject><subject>Ubiquitination</subject><subject>Vaccine</subject><issn>1672-7681</issn><issn>2042-0226</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1UU1P3DAUtCpQ2UJ_QC_IEpdeUvyVOL4gVQhopRVIaDlbTvISTBNnsZNK--95q6XbUomDP57ezPiNh5AvnH3jTJbnSXElZMa4yZiQRbb5QBaCKYGVKA7IghdaZLoo-RH5lNITY3mptPpIjiRnGntyQX5dSTpX_nn2kw-0951LQO9vr7lm1IdHX_kp4SW4CagfhjkAjZDWY0iQaLWhk4sdILWjLjS0gS66ZlutlvcSeXSYo0dODX2fTshh6_oEn1_PY_JwfbW6_JEt725-Xn5fZrXSbMoML9u2NqxsiwpYY1gu8rqqtVK4OV2CY62uctXyUkgDRSkajoUG0zpX51wek4ud7nquBmhqCFN0vV1HP7i4saPz9m0n-Efbjb-tlibHhQJfXwXi-DxDmuzg09aCCzDOyQohucEvzAVCz_6DPo1zDGjPCiWMVDi-RBTfoeo4phSh3Q_Dmd1GaXdRWozSbqO0G-Sc_utiz_iTHQLEDpCwFTqIf59-X_UFv0iqvA</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Song, Xiaoqi</creator><creator>Liu, Shuo</creator><creator>Wang, Wendie</creator><creator>Ma, Zhongfei</creator><creator>Cao, Xuetao</creator><creator>Jiang, Minghong</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200801</creationdate><title>E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells</title><author>Song, Xiaoqi ; Liu, Shuo ; Wang, Wendie ; Ma, Zhongfei ; Cao, Xuetao ; Jiang, Minghong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-918ffc908f6be0d90525cbc744bc7a78ea0f7b54f18239e682d14f17e9faac513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/250/262/2106/2108</topic><topic>631/80/304</topic><topic>631/80/86/2364</topic><topic>Antibodies</topic><topic>Aquatic life</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Double-stranded RNA</topic><topic>Immune response</topic><topic>Immunology</topic><topic>Innate immunity</topic><topic>Interferon regulatory factor 3</topic><topic>Macrophages</topic><topic>Medical Microbiology</topic><topic>Microbiology</topic><topic>NF-κB protein</topic><topic>Phosphates</topic><topic>Proteasomes</topic><topic>TLR3 protein</topic><topic>Toll-like receptors</topic><topic>Ubiquitin</topic><topic>Ubiquitin-protein ligase</topic><topic>Ubiquitination</topic><topic>Vaccine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Xiaoqi</creatorcontrib><creatorcontrib>Liu, Shuo</creatorcontrib><creatorcontrib>Wang, Wendie</creatorcontrib><creatorcontrib>Ma, Zhongfei</creatorcontrib><creatorcontrib>Cao, Xuetao</creatorcontrib><creatorcontrib>Jiang, Minghong</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cellular & molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Xiaoqi</au><au>Liu, Shuo</au><au>Wang, Wendie</au><au>Ma, Zhongfei</au><au>Cao, Xuetao</au><au>Jiang, Minghong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells</atitle><jtitle>Cellular & molecular immunology</jtitle><stitle>Cell Mol Immunol</stitle><addtitle>Cell Mol Immunol</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>17</volume><issue>8</issue><spage>865</spage><epage>874</epage><pages>865-874</pages><issn>1672-7681</issn><eissn>2042-0226</eissn><abstract>Upon recognition of dsRNA, toll-like receptor 3 (TLR3) recruits the adaptor protein TRIF to activate IRF3 and NF-κB signaling, initiating innate immune responses. The ubiquitination of TLR3 downstream signaling molecules and their roles in the innate response have been discovered; however, whether TLR3 itself is ubiquitinated and then functionally involved remains to be elucidated. By immunoprecipitating TLR3-binding proteins in macrophages, we identified ring finger protein 170 (RNF170) as a TLR3-binding E3 ligase. RNF170 mediated the K48-linked polyubiquitination of K766 in the TIR domain of TLR3 and promoted the degradation of TLR3 through the proteasome pathway. The genetic ablation of RNF170 selectively augmented TLR3-triggered innate immune responses both in vitro and in vivo. Our results reveal a novel role for RNF170 in selectively inhibiting TLR3-triggered innate immune responses by promoting TLR3 degradation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31076723</pmid><doi>10.1038/s41423-019-0236-y</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | 631/250/262/2106/2108 631/80/304 631/80/86/2364 Antibodies Aquatic life Biomedical and Life Sciences Biomedicine Double-stranded RNA Immune response Immunology Innate immunity Interferon regulatory factor 3 Macrophages Medical Microbiology Microbiology NF-κB protein Phosphates Proteasomes TLR3 protein Toll-like receptors Ubiquitin Ubiquitin-protein ligase Ubiquitination Vaccine |
| title | E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells |
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