CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling - CityU Scholars

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/><meta name="citation_author_institution" content="China Pharmaceutical University" /><meta name="citation_author" content="Yue Yin" /><meta name="citation_author_institution" content="China Pharmaceutical University" /><meta name="citation_author" content="Jing Sun" /><meta name="citation_author_institution" content="China Pharmaceutical University" /><meta name="citation_author" content="Quanyi Wang" /><meta name="citation_author_institution" content="China Pharmaceutical University" /><meta name="citation_author" content="Lingxiao Xu" /><meta name="citation_author_institution" content="Nanjing Medical University" /><meta name="citation_author" content="Haiyang Hu" /><meta name="citation_author_institution" content="China Pharmaceutical University" /><meta name="citation_author" content="Chen Wang" /><meta name="citation_author_institution" content="China Pharmaceutical University" /><meta name="citation_publication_date" content="2024/02" /><meta name="citation_doi" 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rendering_researchoutput_compact rendering_researchoutput rendering_compact rendering_researchoutput_compact"><h1 class="title">CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling</h1></div><p class="type"><span class="type_family">Research output<span class="type_family_sep">: </span></span><span class="type_classification_parent">Journal Publications and Reviews<span class="type_parent_sep"> › </span></span><span class="type_classification">RGC 21 - Publication in refereed journal</span><span class="type_classification"><span class="type_parent_sep"> › </span>peer-review</span></p></div> <div class="tabs-container"> <ul class="clear"> <li class="selected"><a class="portal_link" href="https://scholars.cityu.edu.hk/en/publications/csnk1a1ck1-suppresses-autoimmunity-by-restraining-the-cgassting1-signaling(85801725-0f10-4493-b724-839d0b1c9b3b).html"><span>Overview</span></a> </li> </ul> </div> <div class="pub-full"> <div class="pub-top"> <div class="view-box scopus"> <span class="number">4</span> <span>Scopus Citations</span> </div> <div class="view-box viewall-scopus"> <a target="_blank" class="view_all_scopus_button" href="https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85171630296&origin=recordpage"> Scopus Metrics </a> </div> <div class="view-box almetric"> <script type="text/javascript" src="//d1bxh8uas1mnw7.cloudfront.net/assets/embed.js"></script> <div class="altmetric-embed pure_altmetric_component" data-badge-type="2" data-badge-popover="left" data-hide-no-mentions="true" data-link-target="true" data-doi="10.1080/15548627.2023.2256135"></div> </div> <div class="graph_viewer"> <div class="graph"><a class="portal_graphviewer_button" href="javascript:void(0);" id="j_id-222676425_40f6ca2e"><span>View graph of relations</span></a> <script type="text/javascript"></script> <i class="icon-network"></i> </div> </div> <div class="addthis"> <div class="addthis_sharing_toolbox"></div> </div> </div> <div class="view-box"> <h2 class="subheader">Author(s)</h2><div class="rendering rendering_researchoutput rendering_researchoutput_associatesauthorsclassifiedsummarizedlistportal rendering_contributiontojournal rendering_associatesauthorsclassifiedsummarizedlistportal rendering_contributiontojournal_associatesauthorsclassifiedsummarizedlistportal"><ul class="relations persons"><li>Mingyu Pan</li><li class="external">Tongyu Hu</li><li class="external">Jiao Lyu</li><li class="external">Yue Yin</li><li class="external">Jing Sun</li><li><a onclick="$(this).up('ul').next('ul').toggleClassName('common_hidden');return false;" href="#" class="all link"><span>And 4 others</span></a></li></ul><ul class="relations persons common_hidden associates_authors_full_list"><li class="external">Quanyi Wang</li><li class="external">Lingxiao Xu</li><li class="external">Haiyang Hu</li><li class="external">Chen Wang</li></ul></div> </div> <div class="view-box"> <h2 class="subheader">Related Research Unit(s)</h2><div class="rendering rendering_researchoutput rendering_researchoutput_associatesorganisationsportal rendering_contributiontojournal rendering_associatesorganisationsportal rendering_contributiontojournal_associatesorganisationsportal"><ul class="relations organisations"><li class="a"><a rel="Organisation" href="https://scholars.cityu.edu.hk/en/organisations/department-of-biomedical-sciences(7f082170-95c7-47b9-b02b-8eaecd285c60).html" class="link"><span>Department of Biomedical Sciences</span></a></li></ul></div> </div> <div class="view-box"> <h2 class="subheader">Detail(s)</h2><div class="rendering rendering_researchoutput rendering_researchoutput_detailsportal rendering_contributiontojournal rendering_detailsportal rendering_contributiontojournal_detailsportal"><div class="article"><table class="properties"><tbody><tr class="language"><th scope="row">Original language</th><td>English</td></tr><tr><th scope="row">Pages (from-to)</th><td>311-328</td></tr><tr><th scope="row">Journal / Publication</th><td><a rel="Journal" href="https://scholars.cityu.edu.hk/en/journals/autophagy(95977567-508e-4b30-9e3b-3027cb835dc3)/publications.html" class="link"><span>Autophagy</span></a></td></tr><tr><th scope="row">Volume</th><td>20</td></tr><tr><th scope="row">Issue number</th><td>2</td></tr><tr><th scope="row">Online published</th><td><span class="date">18 Sept 2023</span></td></tr><tr class="status"><th scope="row">Publication status</th><td><span class="prefix">Published - </span><span class="date">Feb 2024</span></td></tr></tbody></table></div></div> </div> <div class="view-box"> <h2 class="subheader">Link(s)</h2> <table class="properties pub-links"> <tr> <th>DOI</th> <td><div class="rendering rendering_researchoutput rendering_researchoutput_versioneddoiextensionportal rendering_contributiontojournal rendering_versioneddoiextensionportal rendering_contributiontojournal_versioneddoiextensionportal"><h2 class="subheader">DOI</h3><ul class="relations links digital_object_identifiers"><li class="embargo_date_ended available unknown "><a onclick="window.open(this.href, '_blank','noopener,noreferrer'); return false;" href="https://doi.org/10.1080/15548627.2023.2256135" class="link"><span>https://doi.org/10.1080/15548627.2023.2256135</span></a> <p class="dimmed">Final Published version</p></li></ul></div> </td> </tr> <tr> <th></th> <td> <span class="sfx-button" title="Check@CityULib"> <a href="https://julac.hosted.exlibrisgroup.com/primo-explore/openurl?ctx_ver=Z39.88-2004&ctx_tim=2024-11-27T14%3A23%3A48HKT&ctx_enc=info%3Aofi%2FencUTF-8&url_ver=Z39.88-2004&url_ctx_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Actx&rft.genre=article&rft_val_fmt=info%3Aofi%2Fkev%3Afmt%3Ajournal&rfr_id=info%3Asid%2F%3Apure&rft.atitle=CSNK1A1%2FCK1%CE%B1%20suppresses%20autoimmunity%20by%20restraining%20the%20CGAS-STING1%20signaling&rft_id=info%3Adoi%2F10.1080%2F15548627.2023.2256135&rft.aulast=Pan&rft.aufirst=Mingyu&rft.auinit=M&rft.date=2024-02&rft.volume=20&rft.issue=2&rft.issn=1554-8627&rft.jtitle=Autophagy&rft.pages=311-328&institution=CUH_ALMA&vid=CUH" target="_blank"> Check@CityULib </a> </span> </td> </tr> <tr> <th>Link to Scopus</th> <td><a target="_blank" class="scopus-link-pub" href="https://www.scopus.com/record/display.uri?eid=2-s2.0-85171630296&origin=recordpage"> https://www.scopus.com/record/display.uri?eid=2-s2.0-85171630296&origin=recordpage </a></td> </tr> <tr class="permanent_link"> <th>Permanent Link</th> <td> <a href="https://scholars.cityu.edu.hk/en/publications/publication(85801725-0f10-4493-b724-839d0b1c9b3b).html">https://scholars.cityu.edu.hk/en/publications/publication(85801725-0f10-4493-b724-839d0b1c9b3b).html</a></td> </tr> </table> </div> <div class="view-box"> <h2 class="subheader">Abstract</h2><div class="rendering rendering_researchoutput rendering_researchoutput_customabstractportal rendering_contributiontojournal rendering_customabstractportal rendering_contributiontojournal_customabstractportal"><div class="textblock">STING1 (stimulator of interferon response cGAMP interactor 1) is the quintessential protein in the CGAS-STING1 signaling pathway, crucial for the induction of type I IFN (interferon) production and eliciting innate immunity. Nevertheless, the overactivation or sustained activation of STING1 has been closely associated with the onset of autoimmune disorders. Notably, the majority of these disorders manifest as an upregulated expression of type I interferons and IFN-stimulated genes (ISGs). Hence, strict regulation of STING1 activity is paramount to preserve immune homeostasis. Here, we reported that CSNK1A1/CK1α, a serine/threonine protein kinase, was essential to prevent the overactivation of STING1-mediated type I IFN signaling through autophagic degradation of STING1. Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation. Consistently, SSTC3, a selective CSNK1A1 agonist, significantly attenuated the response of the CGAS-STING1 signaling by promoting STING1 autophagic degradation. Importantly, pharmacological activation of CSNK1A1 using SSTC3 markedly repressed the systemic autoinflammatory responses in the <i>trex1</i><sup>-/-</sup> mouse autoimmune disease model and effectively suppressed the production of IFNs and ISGs in the PBMCs of SLE patients. Taken together, our study reveals a novel regulatory role of CSNK1A1 in the autophagic degradation of STING1 to maintain immune homeostasis. Manipulating CSNK1A1 through SSTC3 might be a potential therapeutic strategy for alleviating STING1-mediated aberrant type I IFNs in autoimmune diseases. © 2023 Informa UK Limited, trading as Taylor & Francis Group.</div></div> </div> <div class="view-box"> <h2 class="subheader">Research Area(s)</h2><div class="rendering rendering_keywordable rendering_keywordgroupsexcludecopyright rendering_keywordable_keywordgroupsexcludecopyright"><div class="keywordcontainers"><ul class="relations keywords"><li>Autoimmunity, autophagy, CSNK1A1, STING1, type I IFN</li></ul></div></div> </div> <div class="publication_related_concepts"> <div class="view_preview_panel"><script type="text/javascript" src="/resources/style/js/concept_tooltip.js?stamp=1731905518316"></script> <div class="relationlist for_publication_fingerprints"> <h2 class="section for_publication_fingerprints subheader"> Fingerprint </h2> <p class="portal_inline_help">Publication fingerprints text</p> <div class="concept_listing" 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href="https://scholars.cityu.edu.hk/en/publications/csnk1a1ck1-suppresses-autoimmunity-by-restraining-the-cgassting1-signaling(85801725-0f10-4493-b724-839d0b1c9b3b).ris?download=true"><span>RIS</span></a> ]</span> <span class="publication_export">[ <a class="portal_link" href="https://scholars.cityu.edu.hk/en/publications/csnk1a1ck1-suppresses-autoimmunity-by-restraining-the-cgassting1-signaling(85801725-0f10-4493-b724-839d0b1c9b3b).bibtex?download=true"><span>BibTeX</span></a> ]</span> </div> </div> <div class="citation-container"> <div class="view-box cite"><div class="rendering rendering_researchoutput rendering_researchoutput_standard rendering_contributiontojournal rendering_standard rendering_contributiontojournal_standard"><a rel="ContributionToJournal" href="https://scholars.cityu.edu.hk/en/publications/csnk1a1ck1-suppresses-autoimmunity-by-restraining-the-cgassting1-signaling(85801725-0f10-4493-b724-839d0b1c9b3b).html" class="link"><span><strong>CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling.</strong></span></a> / Pan, Mingyu; Hu, Tongyu; Lyu, Jiao et al. <br />In: <a rel="Journal" href="https://scholars.cityu.edu.hk/en/journals/autophagy(95977567-508e-4b30-9e3b-3027cb835dc3)/publications.html" class="link"><span>Autophagy</span></a>, Vol. 20, No. 2, 02.2024, p. 311-328.<p class="type"><span class="type_family">Research output<span class="type_family_sep">: </span></span><span class="type_classification_parent">Journal Publications and Reviews<span class="type_parent_sep"> › </span></span><span class="type_classification">RGC 21 - Publication in refereed journal</span><span class="type_classification"><span class="type_parent_sep"> › </span>peer-review</span></p></div> </div> <div class="view-box cite" style="display: none;"><div class="rendering rendering_researchoutput rendering_researchoutput_harvard rendering_contributiontojournal rendering_harvard rendering_contributiontojournal_harvard">Pan, M, Hu, T, Lyu, J, Yin, Y, Sun, J, Wang, Q, Xu, L, Hu, H & Wang, C 2024, '<a rel="ContributionToJournal" href="https://scholars.cityu.edu.hk/en/publications/csnk1a1ck1-suppresses-autoimmunity-by-restraining-the-cgassting1-signaling(85801725-0f10-4493-b724-839d0b1c9b3b).html" class="link harvard_title"><span>CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling</span></a>', <a rel="Journal" href="https://scholars.cityu.edu.hk/en/journals/autophagy(95977567-508e-4b30-9e3b-3027cb835dc3)/publications.html" class="link"><span><em>Autophagy</em></span></a>, vol. 20, no. 2, pp. 311-328. <a onclick="window.open(this.href, '_blank','noopener,noreferrer'); return false;" href="https://doi.org/10.1080/15548627.2023.2256135" class="link"><span>https://doi.org/10.1080/15548627.2023.2256135</span></a></div> </div> <div class="view-box cite" style="display: none;"><div class="rendering rendering_researchoutput rendering_researchoutput_apa rendering_contributiontojournal rendering_apa rendering_contributiontojournal_apa">Pan, M., Hu, T., Lyu, J., Yin, Y., Sun, J., Wang, Q., Xu, L., Hu, H., & Wang, C. (2024). <a rel="ContributionToJournal" href="https://scholars.cityu.edu.hk/en/publications/csnk1a1ck1-suppresses-autoimmunity-by-restraining-the-cgassting1-signaling(85801725-0f10-4493-b724-839d0b1c9b3b).html" class="link"><span>CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling</span></a>. <a rel="Journal" href="https://scholars.cityu.edu.hk/en/journals/autophagy(95977567-508e-4b30-9e3b-3027cb835dc3)/publications.html" class="link"><span><em>Autophagy</em></span></a>, <em>20</em>(2), 311-328. <a onclick="window.open(this.href, '_blank','noopener,noreferrer'); return false;" href="https://doi.org/10.1080/15548627.2023.2256135" class="link"><span>https://doi.org/10.1080/15548627.2023.2256135</span></a></div> </div> <div class="view-box cite" style="display: none;"><div class="rendering rendering_researchoutput rendering_researchoutput_vancouver rendering_contributiontojournal rendering_vancouver rendering_contributiontojournal_vancouver">Pan M, Hu T, Lyu J, Yin Y, Sun J, Wang Q et al. <span class="title"><a rel="ContributionToJournal" href="https://scholars.cityu.edu.hk/en/publications/csnk1a1ck1-suppresses-autoimmunity-by-restraining-the-cgassting1-signaling(85801725-0f10-4493-b724-839d0b1c9b3b).html" class="link"><span>CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling</span></a></span>. <a rel="Journal" href="https://scholars.cityu.edu.hk/en/journals/autophagy(95977567-508e-4b30-9e3b-3027cb835dc3)/publications.html" class="link"><span>Autophagy</span></a>. 2024 Feb;20(2):311-328. Epub 2023 Sept 18. doi: 10.1080/15548627.2023.2256135</div> </div> <div class="view-box cite" style="display: none;"><div class="rendering rendering_researchoutput rendering_researchoutput_author rendering_contributiontojournal rendering_author rendering_contributiontojournal_author">Pan, Mingyu ; Hu, Tongyu ; Lyu, Jiao et al. / <a rel="ContributionToJournal" href="https://scholars.cityu.edu.hk/en/publications/csnk1a1ck1-suppresses-autoimmunity-by-restraining-the-cgassting1-signaling(85801725-0f10-4493-b724-839d0b1c9b3b).html" class="link"><span><strong>CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling</strong></span></a>. In: <a rel="Journal" href="https://scholars.cityu.edu.hk/en/journals/autophagy(95977567-508e-4b30-9e3b-3027cb835dc3)/publications.html" class="link"><span>Autophagy</span></a>. 2024 ; Vol. 20, No. 2. pp. 311-328.</div> </div> </div> </div> </div> </div> </div> <div class="footer"> <div class="wrapper"> <div class="cityu-scholar-footer-outbox"> <div class="cityu-scholar-footer-inbox"> <a href="https://www.cityu.edu.hk/cityu/privacy/index.htm" title="Footer Privacy Policy" target="_blank">Privacy Policy</a> | <a href="https://www.cityu.edu.hk/cityu/copyright/index.htm#copyright" title="Footer Copyright" target="_blank">Copyright</a> | <a href="https://www.cityu.edu.hk/cityu/disclaimer/index.htm#disclaimer" title="Footer Disclaimer" target="_blank">Disclaimer</a> | <a href="https://www.cityu.edu.hk/cityu/accessibility/" title="Footer Accessibility" target="_blank">Accessibility</a> | <a href="https://www.cityu.edu.hk/cityu/contactus/index.htm" title="Footer Contact Us" target="_blank">Contact Us</a><br /> © City University of Hong Kong. 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CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling - CityU Scholars | A Research Hub of Excellence