{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:23:35Z","timestamp":1792268615689,"version":"4.4.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,11,11]]},"abstract":"<jats:p>\n                    Microtubule-associated protein 1A\/1B-light chain 3 (LC3)-associated phagocytosis (LAP) plays a critical role in host defense against invading pathogens, including\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Listeria<\/jats:italic>\n                      monocytogenes (\n                      <jats:italic toggle=\"yes\">Listeria. monocytogenes<\/jats:italic>\n                      )\n                    <\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">\n                        Salmonella typhimurium (\n                        <jats:italic toggle=\"yes\">S. typhimurium<\/jats:italic>\n                        )\n                      <\/jats:italic>\n                    <\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">\n                      Francisella novicida (\n                      <jats:italic toggle=\"yes\">F. novicida<\/jats:italic>\n                      )\n                    <\/jats:italic>\n                    . However, the precise regulatory mechanisms controlling LAP remain poorly understood. Here, we identify enkurin domain-containing protein 1 (ENKD1) as a key negative regulator of LAP during infection with these pathogens. Macrophages infected with\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">L.<\/jats:italic>\n                      monocytogenes\n                    <\/jats:italic>\n                    (10403S),\n                    <jats:italic toggle=\"yes\">S. typhimurium<\/jats:italic>\n                    (ATCC14028), or\n                    <jats:italic toggle=\"yes\">F. novicida<\/jats:italic>\n                    (U112) exhibit significant ENKD1 downregulation. ENKD1-deficient macrophages display enhanced antibacterial activity, characterized by increased LAP, higher reactive oxygen species production, enhanced LC3 lipidation on phagosomes, and improved phagosome-lysosome fusion. In vivo, ENKD1\n                    <jats:italic toggle=\"yes\">-<\/jats:italic>\n                    deficient mice\n                    <jats:italic toggle=\"yes\">ex<\/jats:italic>\n                    hibited improved bacterial clearance in the liver and spleen, with notable survival benefits. Mechanistically, ENKD1 interacts with the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21), which mediates degradation of Run domain Beclin-1-interacting and cysteine-rich domain-containing protein (RUBCN) through K48-linked polyubiquitination, thereby dampening RUBCN\u2019s role in LAP. Our findings reveal an ENKD1\u2013TRIM21\u2013RUBCN axis that suppresses LAP, providing insights into antibacterial immune regulation and suggesting potential therapeutic strategies to enhance host defense against intracellular pathogens.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2501953122","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T17:46:47Z","timestamp":1762278407000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["ENKD1 attenuates antibacterial immunity by facilitating TRIM21-mediated RUBCN degradation to suppress LC3-associated phagocytosis"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5275-9608","authenticated-orcid":false,"given":"Caimeng","family":"Song","sequence":"first","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5946-7770","authenticated-orcid":false,"given":"Lulu","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5166-8608","authenticated-orcid":false,"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6754-2440","authenticated-orcid":false,"given":"Shujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-6676","authenticated-orcid":false,"given":"Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-7804","authenticated-orcid":false,"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University","place":["Jinan, China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-0549","authenticated-orcid":false,"given":"Tianliang","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-1907","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University","place":["Jinan, 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Song ENKD1 attenuates antibacterial immunity by facilitating TRIM21-mediated RUBCN degradation to suppress LC3 associated phagocytosis. ProteomeXchange. https:\/\/proteomecentral.proteomexchange.org\/cgi\/GetDataset?ID=PXD069653. Deposited 20 October 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2501953122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T17:47:12Z","timestamp":1762278432000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2501953122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":37,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2025,11,11]]}},"alternative-id":["10.1073\/pnas.2501953122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2501953122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"2025-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2501953122"}}