{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T03:40:41Z","timestamp":1794109241626,"version":"4.8.0"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"14","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["U54CA244719"],"award-info":[{"award-number":["U54CA244719"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["I-1389"],"award-info":[{"award-number":["I-1389"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP180725"],"award-info":[{"award-number":["RP180725"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI005284"],"award-info":[{"award-number":["T32AI005284"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,4,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The cGAS-STING pathway is important for immune defense against infection and cancer. STING activation triggers multiple signaling cascades leading to activation of IRF3, NF-\u03baB, and autophagy. By generating mice harboring mutations of STING that specifically inactivate different signaling cascades, we found that ablation of IRF3 activation, which is essential for the induction of type I interferons, was not sufficient to abolish the immune defense against virus infection and cancer in mouse models. Rather, impairing the ability of STING to recruit TBK1, which is important for activating both IRF3 and NF-\u03baB, abolished the immune defense functions of STING. These results demonstrate that the recruitment of TBK1 to STING has functions that are broader than activating IRF3 and inducing type I interferons.<\/jats:p>","DOI":"10.1073\/pnas.2100225118","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T15:40:29Z","timestamp":1617118829000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":603,"title":["TBK1 recruitment to STING activates both IRF3 and NF-\u03baB that mediate immune defense against tumors and viral infections"],"prefix":"10.1073","volume":"118","author":[{"given":"Seoyun","family":"Yum","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;"},{"name":"Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-2691","authenticated-orcid":false,"given":"Minghao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;"},{"name":"Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1275-8276","authenticated-orcid":false,"given":"Yan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;"},{"name":"Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-8251","authenticated-orcid":false,"given":"Zhijian J.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;"},{"name":"Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148;"},{"name":"HHMI, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07317"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.09.003"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900850106"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232458"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1229963"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1006-9"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-018-0251-z"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1000-2"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002521"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2630"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00037-14"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.056"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.037"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.053"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1801233115"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1605-5"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.022"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.029"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244040"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08476"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13348"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.4.663"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60893"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.017"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cancerbio-030518-055636"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.031"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512832112"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.07.008"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25432"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.009"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17156-x"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00999-10"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1621363114"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804277"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0365"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-844548"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.2.898-904.1996"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.8.6380-6386.1999"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005201108"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.4049\/jimmunol.163.9.4859","article-title":"4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses","volume":"163","author":"Tan J. T.","year":"1999","unstructured":"J. T. Tan, J. K. Whitmire, R. Ahmed, T. C. Pearson, C. P. Larsen, 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. J. Immunol. 163, 4859\u20134868 (1999).","journal-title":"J. Immunol."},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2937"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403555101"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2674"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.12.8604"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.142"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18268"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.3.1319"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh391"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-014-0045-x"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00402"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0677"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-3614"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1613187113"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.019"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35412"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1159\/000450705"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3850"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171351"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05245"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600722"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.9.4288-4295.1990"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks042"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2100225118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2100225118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T08:09:02Z","timestamp":1698134942000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2100225118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,30]]},"references-count":64,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2021,4,6]]}},"alternative-id":["10.1073\/pnas.2100225118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2100225118","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.739858439.793587585","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.739858439.793585742","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,30]]},"assertion":[{"value":"2021-03-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2100225118"}}