ArticleMolecular and cellular biology2017
Obesity-Linked Phosphorylation of SIRT1 by Casein Kinase 2 Inhibits Its Nuclear Localization and Promotes Fatty Liver.
Article in Molecular and cellular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Microglial protein kinase CK2 prevents obesity in mice potentially through NLRP3 inflammasome activation.Nature communications · 2026Article
- N-terminal thrombospondin-1 enhances muscle function and tissue-specific metabolic adaptation in response to exercise and cold exposure.Experimental & molecular medicine · 2026Article
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- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.MedComm · 2024Review
- Inhibitory protein-protein interactions of the SIRT1 deacetylase are choreographed by post-translational modification.Protein science : a publication of the Protein Society · 2024Article
- Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency.iScience · 2023Article
- Identification of common signature genes and pathways underlying the pathogenesis association between nonalcoholic fatty liver disease and atherosclerosis.Frontiers in cardiovascular medicine · 2023Article
- Role of Post-translational Modification of Silent Mating Type Information Regulator 2 Homolog 1 in Cancer and Other Disorders.Journal of cancer prevention · 2022Review
- The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review.Journal of developmental biology · 2022Review
- The phosphorylation to acetylation/methylation cascade in transcriptional regulation: how kinases regulate transcriptional activities of DNA/histone-modifying enzymes.Cell & bioscience · 2022Review
- JNK-mediated Ser27 phosphorylation and stabilization of SIRT1 promote growth and progression of colon cancer through deacetylation-dependent activation of Snail.Molecular oncology · 2022Article
- Depletion of mitochondrial methionine adenosyltransferase α1 triggers mitochondrial dysfunction in alcohol-associated liver disease.Nature communications · 2022Article
- Regulation of SIRT1 and Its Roles in Inflammation.Frontiers in immunology · 2022Review
- Redox-sensitive activation of CCL7 by BRG1 in hepatocytes during liver injury.Redox biology · 2021Article
- Protein acetylation: a novel modus of obesity regulation.Journal of molecular medicine (Berlin, Germany) · 2021Review
- The Emerging Role of Stress Granules in Hepatocellular Carcinoma.International journal of molecular sciences · 2021Review
- ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2.Molecules (Basel, Switzerland) · 2021Article
- Loss of SIRT1 in diabetes accelerates DNA damage-induced vascular calcification.Cardiovascular research · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including nonalcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase 2 (CK2), the levels of which were dramatically elevated in obesity. Mechanistically, phosphorylation of SIRT1 at Ser-164 substantially inhibited its nuclear localization and modestly affected its deacetylase activity. Adenovirus-mediated liver-specific expression of SIRT1 or a phosphor-defective S164A-SIRT1 mutant promoted fatty acid oxidation and ameliorated liver steatosis and glucose intolerance in diet-induced obese mice, but these beneficial effects were not observed in mice expressing a phosphor-mimic S164D-SIRT1 mutant. Remarkably, phosphorylated S164-SIRT1 and CK2 levels were also highly elevated in liver samples of NAFLD patients and correlated with disease severity. Thus, inhibition of phosphorylation of SIRT1 by CK2 may serve as a new therapeutic approach for treatment of NAFLD and other obesity-related diseases.
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Registered trials
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