ArticleNature communications2023
Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13citing papers in PubMed
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Nitric oxide drives proteomic diversity through alternative splicing.Molecular cell · 2026Article
- Proteome-wide profiling of S-nitrosylated proteins using the SNOTRAP probe and mass spectrometry-based detection.Nature protocols · 2026Review
- Nitric oxide induces p53-mediated cell death in human nasal epithelial cells.Scientific reports · 2026Article
- Aberrant Protein S-Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases.Journal of neurochemistry · 2026Review
- Aberrant S-nitrosylation in the TCA cycle contributes to mitochondrial dysfunction, energy compromise, and synapse loss in neurodegenerative diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Nitric oxide‑mediated S‑Nitrosylation contributes to signaling transduction in human physiological and pathological status (Review).International journal of molecular medicine · 2025Review
- Effects of Environmental Non-Essential Toxic Heavy Metals on Epigenetics During Development.Toxics · 2025Review
- The evolution of S-nitrosylation detection methodology and the role of protein S-nitrosylation in various cancers.Cancer cell international · 2024Review
- Epigenetic Regulation of CXC Chemokine Expression by Environmental Electrophiles Through DNA Methyltransferase Inhibition.International journal of molecular sciences · 2024Article
- A Comprehensive Review of Various Therapeutic Strategies for the Management of Skin Cancer.ACS omega · 2024Review
- Early life adversity drives sex-dependent changes in 5-mC DNA methylation of parvalbumin cells in the prefrontal cortex in rats.bioRxiv : the preprint server for biology · 2024Article
- Prognostic analysis of patients with gastric cancer based on NFrontiers in pharmacology · 2024Article
- G6PD Orchestrates Genome-Wide DNA Methylation and Gene Expression in the Vascular Wall.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
30 authors at 10 institutions in 2 countries.
Kosaku Okuda *Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Kengo Nakahara *Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.ORCID 0000-0003-0765-4931
Akihiro Ito *Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.ORCID 0000-0003-0908-8929
Yuta IijimaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Ryosuke NomuraDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Ashutosh KumarLaboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, Yokohama, Kanagawa, Japan.
Kana FujikawaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Kazuya AdachiDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Yuki ShimadaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Satoshi FujioDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Reina YamamotoDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Nobumasa TakasugiDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.ORCID 0000-0002-6059-2082
Kunishige OnumaDivision of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Mitsuhiko OsakiDivision of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Futoshi OkadaDivision of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Taichi UkegawaDepartment of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Yasuo TakeuchiDepartment of Synthetic and Medicinal Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Norihisa YasuiLaboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.ORCID 0000-0001-7117-3070
Atsuko YamashitaLaboratory of Structural Biology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.ORCID 0000-0002-8001-4642
Hiroyuki MarusawaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yosuke MatsushitaDivision of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Tokushima, Japan.
Toyomasa KatagiriDivision of Genome Medicine, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Tokushima, Japan.
Takahiro ShibataGraduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.ORCID 0000-0003-3194-607X
Koji UchidaLaboratory of Food Chemistry, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Sheng-Yong NiuBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nhi B LangNeurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-7187-1194
Tomohiro NakamuraNeurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-4246-7771
Kam Y J ZhangLaboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, Yokohama, Kanagawa, Japan.ORCID 0000-0002-9282-8045
Stuart A LiptonNeurodegeneration New Medicines Center, and Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, La Jolla, CA, USA. slipton@scripps.edu.ORCID 0000-0002-3490-1259
Takashi UeharaDepartment of Medicinal Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan. uehara-t@okayama-u.ac.jp.ORCID 0000-0002-8545-4006
Okayama University · JPScripps Research Institute · USTottori University · JPRIKEN Center for Biosystems Dynamics Research · JPTokushima University · JPBroad Institute · USKyoto University · JPNagoya University · JPThe University of Tokyo · JPTokyo University of Pharmacy and Life Sciences · JP
Funding
Novel Proteomics Approach to HIV-Associated Neurocognitive Disorder & Drug AbuseDP1DA041722 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2016 to 2020
$7.0MLeadership in AD/ADRD Drug DiscoveryR35AG071734 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2021 to 2025
$5.4MDynamic Interactions of the S-Nitrosoproteome in Type 2 Diabetes/Metabolic Syndrome and Alzheimer’s DiseaseRF1AG057409 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2020
$4.1MS-Nitrosylation-Induced Posttranslational Modification and Aberrant Cell Signaling in Sporadic Alzheimer's DiseaseR01AG056259 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2021
$3.3MNeuroprotective Mechanisms of S-Nitrosylated ApoE2 in Aging and Alzheimer's DiseaseR01AG061845 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI NAKAMURA, TOMOHIRO · 2018 to 2022
$2.4MCrosstalk between innate-immunity human microglia and adaptive-immunity Tregs in Alzheimer's diseaseR01AG078756 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI STUART A LIPTON · 2022 to 2026
$2.3MIdentification and Verification of S-Nitrosylated Proteins in Bodily Fluids as Biomarkers for Parkinson's Disease and Lewy Body DementiaR61NS122098 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI NAKAMURA, TOMOHIRO · 2021 to 2021
$2.2MS-Nitrosylation-Dependent Pathological Spread of Abnormal Proteins in Frontotemporal Dementia and Lewy Body DementiaRF1NS123298 · NINDS · SCRIPPS RESEARCH INSTITUTE, THE · PI NAKAMURA, TOMOHIRO · 2021 to 2021
$2.1MNIA NIH HHS R01 AG056259NIA NIH HHS R01 AG061845NIA NIH HHS R01 AG078756NIA NIH HHS R35 AG071734NIA NIH HHS RF1 AG057409NIDA NIH HHS DP1 DA041722NINDS NIH HHS R61 NS122098NINDS NIH HHS RF1 NS123298
Abstract
DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-L-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include Cyclin D2 (Ccnd2), which is required for neoplastic cell proliferation in some tumor types. In cell-based and in vivo cancer models, only DNMT3B enzymatic activity, and not DNMT1 or DNMT3A, affects Ccnd2 expression. Using structure-based virtual screening, we discovered chemical compounds that specifically inhibit S-nitrosylation without directly affecting DNMT3B enzymatic activity. The lead compound, designated DBIC, inhibits S-nitrosylation of DNMT3B at low concentrations (IC
Indexed as
DNA (Cytosine-5-)-MethyltransferasesEpigenesis, GeneticAnimalsCell Transformation, NeoplasticDNA (Cytosine-5-)-Methyltransferase 1DNA MethylationDNA Methyltransferase 3BDNA Modification MethylasesHumansMiceDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BDNA Modification Methylases
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