{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:33:21Z","timestamp":1790422401158,"version":"4.1.0"},"reference-count":41,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"15","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AA029723"],"award-info":[{"award-number":["R01AA029723"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013015","name":"Cedars Sinai Medical Center","doi-asserted-by":"crossref","award":["IRP GREAT 400172"],"award-info":[{"award-number":["IRP GREAT 400172"]}],"id":[{"id":"10.13039\/100013015","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,4,10]]},"abstract":"<jats:p>Alcohol-associated liver disease (ALD) remains a major public health challenge with limited treatment options. NF-\u03baB\u2013driven inflammation in Kupffer cells (KCs) plays a central role in ALD, but the upstream regulators remain poorly understood. Here, we identify the tyrosine kinase SRC as a key mediator of ALD. Chronic ethanol exposure activates SRC in KCs, which directly phosphorylates ubiquitin-conjugating enzyme 9 (UBC9), the only E2 SUMO enzyme, at tyrosine-68 (Y68). This modification enhances NF-\u03baB signaling and increases proinflammatory cytokines (TNF-\u03b1, IL-6, and IL-1\u03b2). These cytokines then promote hepatic lipogenesis through SREBP1c- and CEBP\u03b2-dependent induction of FASN and ACC. Inhibition of UBC9 phosphorylation by gene editing or SRC inhibitor reduces NF-\u03baB\u2013dependent inflammation and lessens ethanol-induced liver injury in mouse models. These findings uncover a previously unrecognized SRC\u2013UBC9\u2013NF-\u03baB axis that drives inflammation in ALD and highlight it as a potential therapeutic target in liver disease.<\/jats:p>","DOI":"10.1126\/sciadv.aec0138","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T18:01:06Z","timestamp":1775844066000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["SRC-mediated phosphorylation of UBC9 regulates inflammatory and metabolic signaling in alcohol-associated liver disease"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6880-8095","authenticated-orcid":true,"given":"Swati","family":"Chandla","sequence":"first","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048 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