{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:09:27Z","timestamp":1788768567051,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"50","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>p300 is an acetyltransferase that regulates gene expression by acetylating histones and transactivating some transcription factors such as nuclear Factor Kappa B (NF\u2010\u03baB) and interferon regulatory factor 3 (IRF3). p53 is an interferon (IFN)\u2010inducible tumor suppressor that enhances antiviral responses. How p300 and p53 precisely regulate innate antiviral immunity remains incompletely understood. Herein, we report that conditional p300 knockout in alveolar epithelial cells does not suppress but rather enhances antiviral responses in mice infected with vesicular stomatitis virus (VSV) and herpes simplex virus (HSV\u20101). In vitro investigation reveals that A\u2010485, a p300\u2010specific inhibitor, and p300 knockdown suppress virus replication but promote IFN\u2010\u03b2 production in a variety of cell types by enhancing (TANK\u2010binding kinase 1) TBK1 and IRF3 phosphorylation. p300 binds TBK1 and acetylates two lysine residues at 241 and 692 to block its activation. p300 expression is downregulated by viral infection in a p53\u2010dependent manner. Mechanistically, viral infection increases the levels of p53, which leads to the upregulation of the seven in absentia homolog 1 (SIAH1) E3 ubiquitin ligase. SIAH1 induces p300 K48\u2010linked polyubiquitination and subsequent proteasomal degradation. Consistently, p53 knockout inhibits, whereas SIAH overexpression enhances antiviral responses. Taken together, our study identifies p300 as an acetyltransferase that suppresses innate immunity by acetylating TBK1, and demonstrates that the p53\u2010SIAH1 axis downregulates p300 to sustain antiviral responses.<\/jats:p>","DOI":"10.1002\/advs.76101","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:02:48Z","timestamp":1781524968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["p300 Degradation by the p53\u2010SIAH1 Axis Relieves TBK1 Acetylation to Enhance Innate Antiviral Immunity"],"prefix":"10.1002","volume":"13","author":[{"given":"Huidi","family":"Yu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Institute of Comparative Medicine Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Zhan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Institute of Comparative Medicine Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiang","family":"Pan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Institute of Comparative Medicine Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penggang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Institute of Comparative Medicine Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Institute of Comparative 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