biostudies-literaturePan JFundamental Research Funds for the Central UniversitiesNatural Science Foundation of Shandong ProvinceNational Science Foundation of ChinaNon-profit Central Research Institute Fund of Chinese Academy of Medical SciencesTaishan Scholarship0823https://www.ebi.ac.uk/biostudies/studies/S-EPMC12352791biostudies-literatureUnknown8Alcoholic cardiomyopathy (ACM) is a type of dilated cardiomyopathy unrelated to ischemia, which develops as a consequence of chronic alcohol consumption. While ethanol-induced irreversible cardiomyocyte death is implicated in ACM development and progression, the precise molecular mechanisms involved are still obscure. In the current study, we demonstrate that ethanol exposure promotes receptor-interacting serine/threonine-protein kinase 1 (RIPK1) autophosphorylation and enhances pRIPK1-associated apoptosis and necroptosis in ACM models both in vivo and in vitro. Through co-immunoprecipitation (Co-IP) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we identified ubiquitin-specific protease 53 (USP53) as a pivotal deubiquitinase involved in modulating RIPK1 Research (Washington, D.C.)USP53 Drives Ethanol-Induced Myocardial Injury by Promoting K63 Deubiquitination-Dependent RIPK1 Activation at K377.PMC123527912022HWYQ-053tsqn202306035ZR2022QH2622023-PT320-062023HWYQ-048ZR2024MH154ZR2022QH0052023QNTD003822717578240052582200660Liu XLi XYuan CPan JDai SWang SZhang MLiu DZhao YLiu FWang LfalseUSP53 Drives Ethanol-Induced Myocardial Injury by Promoting K63 Deubiquitination-Dependent RIPK1 Activation at K377.Alcoholic cardiomyopathy (ACM) is a type of dilated cardiomyopathy unrelated to ischemia, which develops as a consequence of chronic alcohol consumption. While ethanol-induced irreversible cardiomyocyte death is implicated in ACM development and progression, the precise molecular mechanisms involved are still obscure. In the current study, we demonstrate that ethanol exposure promotes receptor-interacting serine/threonine-protein kinase 1 (RIPK1) autophosphorylation and enhances pRIPK1-associated apoptosis and necroptosis in ACM models both in vivo and in vitro. Through co-immunoprecipitation (Co-IP) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we identified ubiquitin-specific protease 53 (USP53) as a pivotal deubiquitinase involved in modulating RIPK1 2025-01-01T00:00:00Z20252026-05-29T16:32:24.408Z2026-04-08T05:25:39.24ZS-EPMC123527914082212710.34133/research.0823