ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018
SUMOylation regulates cytochrome P450 2E1 expression and activity in alcoholic liver disease.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Valorization of Sardinian Grapevine Leaves as a Sustainable Source of Flavonols with Anticancer Potential.Antioxidants (Basel, Switzerland) · 2026Article
- SRC-mediated phosphorylation of UBC9 regulates inflammatory and metabolic signaling in alcohol-associated liver disease.Science advances · 2026Article
- Ubc9-Mediated SUMOylation of RPL3, an Unappreciated Mechanism against Hepatocyte Senescence by Repressing the DHX9-p16 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver.Journal of xenobiotics · 2025Article
- Article
- E3 ubiquitin ligase TRIM2 identified as a novel suppressor of CYP11B2 and aldosterone production.Cellular and molecular life sciences : CMLS · 2024Article
- Sumoylation of methionine adenosyltransferase alpha 1 promotes mitochondrial dysfunction in alcohol-associated liver disease.Hepatology (Baltimore, Md.) · 2024Article
- Abnormal protein SUMOylation in liver disease: novel target for therapy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- The impact of abstinence from chronic alcohol consumption on the mouse striatal proteome: sex and subregion-specific differences.Frontiers in pharmacology · 2024Article
- Mycobacteria modulate SUMOylation to suppresses protective responses in dendritic cells.PloS one · 2023Article
- Review
- Review
- Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice.Molecular medicine reports · 2021Article
- RNA sequencing (RNA-seq) analysis of gene expression provides new insights into hindlimb unloading-induced skeletal muscle atrophy.Annals of translational medicine · 2020Article
- The Role of FAT10 in Alcoholic Hepatitis Pathogenesis.Biomedicines · 2020Review
- Microarray Analysis of Gene Expression Provides New Insights Into Denervation-Induced Skeletal Muscle Atrophy.Frontiers in physiology · 2019Article
- Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Alcohol acts through numerous pathways leading to alcoholic liver disease (ALD). Cytochrome P450 (CYP2E1), an ethanol-inducible enzyme, metabolizes ethanol-producing toxic reactive oxygen species (ROS) and is regulated at the posttranslational level. Small ubiquitin-like modifier (SUMO)ylation is a posttranslational modification that involves the addition of SUMOs, which modulate protein stability, activity, and localization. We demonstrated that ubiquitin-conjugation enzyme 9, the SUMO-conjugating enzyme, is induced in the livers of an intragastric ethanol mouse model. Our aim is to examine whether SUMOylation could regulate ethanol-induced CYP2E1 expression in ALD and to elucidate the molecular mechanism(s). CYP2E1 and UBC9 expression in vitro and in vivo was detected by real-time PCR and immunoblotting/immunostaining. SUMOylation was assayed by mass spectrometry and coimmunoprecipitation. Ubc9 expression was induced in ethanol-fed mouse livers, and silencing inhibited ethanol-mediated CYP2E1 microsomal retention and enzymatic activity. CYP2E1 SUMOylation was found to be induced by ethanol in vitro and in vivo. Ubc9 silencing prevents ethanol-induced lipid accumulation and ROS production. UBC9 was highly expressed in human ALD livers. Finally, we found that lysine 410 is a key SUMOylated residue contributing to CYP2E1 protein stability and activity preventing CYP2E1 SUMOylation. Ethanol-mediated up-regulation of CYP2E1 via SUMOylation enhancing its protein stability and activity and may have important implications in ALD.-Tomasi, M. L., Ramani, K., Ryoo, M., Cossu, C., Floris, A., Murray, B. J., Iglesias-Ara, A., Spissu, Y., Mavila, N. SUMOylation regulates cytochrome P450 2E1 expression and activity in alcoholic liver disease.
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Registered trials
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