{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:21:43Z","timestamp":1793298103499,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IFN regulatory factors play a pivotal role in many cellular processes, including inflammatory and immune responses. Their activation is tightly regulated by TANK-binding kinase 1 (TBK1). In response to microbial components, TBK1 activates IFN regulatory factor 3 (IRF3) and cytokine expression. In this article, we show that TBK1 is a novel target of the IpaH4.5 protein, a Shigella type III effector possessing E3 ubiquitin ligase activity. Remarkably, IpaH4.5 interacts with TBK1 and promotes its K48-linked polyubiquitylation. Consequently, polyubiquitylated TBK1 undergoes proteasome-dependent degradation, which perturbs the phosphorylation, nuclear translocation, and activation of IRF3. Because IRF3 and TBK1 are required for restricting Shigella growth, we propose that the polyubiquitylation and degradation of TBK1 during Shigella infection are new bacterial strategies to modulate the host antibacterial responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1501045","type":"journal-article","created":{"date-parts":[[2015,12,24]],"date-time":"2015-12-24T04:04:53Z","timestamp":1450929893000},"page":"1199-1208","source":"Crossref","is-referenced-by-count":48,"title":["Bacterial E3 Ubiquitin Ligase IpaH4.5 of <i>Shigella flexneri<\/i> Targets TBK1 To Dampen the Host Antibacterial Response"],"prefix":"10.1093","volume":"196","author":[{"given":"Zirui","family":"Zheng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology , Beijing 100850 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congwen","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology , Beijing 100850 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Guan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology , Beijing 100850 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Central Laboratory of Binhu Hospital, The Third Affiliated Hospital of Anhui Medical University , Hefei 230601 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology , Beijing 100850 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology , Beijing 100850 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology , Beijing 100850 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9024-4628","authenticated-orcid":false,"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Hospital Infection Control, The 309th Hospital of Chinese People\u2019s Liberation Army , Beijing 100091 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology , Beijing 100850 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology , Beijing 100850 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,2,1]]},"reference":[{"key":"2025030702123935900_r1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nature10429","article-title":"STING is a direct innate immune sensor of cyclic di-GMP","volume":"478","author":"Burdette","year":"2011","journal-title":"Nature"},{"key":"2025030702123935900_r2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"2025030702123935900_r3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/sj.cr.7290309","article-title":"The host type I interferon response to viral and bacterial infections","volume":"15","author":"Perry","year":"2005","journal-title":"Cell Res."},{"key":"2025030702123935900_r4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/oxfordjournals.jbchem.a022753","article-title":"Analyses of virus-induced homomeric and heteromeric protein associations between IRF-3 and coactivator CBP\/p300","volume":"128","author":"Suhara","year":"2000","journal-title":"J. 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