ArticleNature communications2021
SPOP mutation induces DNA methylation via stabilizing GLP/G9a.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 69 citations in OpenAlex.
- Trigger-day hCG effects on DNA methylation and neurodevelopment in ART offspring.Nature communications · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Systematic investigation of zinc finger MYND-type containing 11-mediated alternative splicing reveals notable events in prostate cancer.Asian journal of urology · 2026Article
- Article
- Sequence rules for a long SPOP-binding degron required for protein ubiquitylation.The Biochemical journal · 2025Article
- Harnessing the SPOP E3 Ubiquitin Ligase via a Bridged Proteolysis Targeting Chimera (PROTAC) Strategy for Targeted Protein Degradation.Journal of medicinal chemistry · 2025Article
- Cul3 substrate adaptor SPOP targets Nup153 for degradation.Molecular biology of the cell · 2025Article
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
- Histone lysine methylation modifiers controlled by protein stability.Experimental & molecular medicine · 2024Review
- Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome.American journal of human genetics · 2024Article
- Review
- Discovery of the First-in-Class G9a/GLP PROTAC Degrader.Journal of medicinal chemistry · 2024Article
- Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis.Journal of hematology & oncology · 2024Review
- Discovery of the First-in-class G9a/GLP PROTAC Degrader.bioRxiv : the preprint server for biology · 2024Article
- Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies.Acta pharmaceutica Sinica. B · 2024Review
- The Role and Mechanism of the Histone Methyltransferase G9a in Tumors: Update.OncoTargets and therapy · 2024Review
- A lncRNA from the FTO locus acts as a suppressor of the mMolecular cell · 2023Article
- Demethylation of EHMT1/GLP Protein Reprograms Its Transcriptional Activity and Promotes Prostate Cancer Progression.Cancer research communications · 2023Article
- Euchromatic histone lysine methyltransferase 2 facilitates radioresistance in prostate cancer by repressing endoplasmic reticulum protein 29 transcription.The Kaohsiung journal of medical sciences · 2023Article
- Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in SPOP E3 ligase gene are reportedly associated with genome-wide DNA hypermethylation in prostate cancer (PCa) although the underlying mechanisms remain elusive. Here, we demonstrate that SPOP binds and promotes polyubiquitination and degradation of histone methyltransferase and DNMT interactor GLP. SPOP mutation induces stabilization of GLP and its partner protein G9a and aberrant upregulation of global DNA hypermethylation in cultured PCa cells and primary PCa specimens. Genome-wide DNA methylome analysis shows that a subset of tumor suppressor genes (TSGs) including FOXO3, GATA5, and NDRG1, are hypermethylated and downregulated in SPOP-mutated PCa cells. DNA methylation inhibitor 5-azacytidine effectively reverses expression of the TSGs examined, inhibits SPOP-mutated PCa cell growth in vitro and in mice, and enhances docetaxel anti-cancer efficacy. Our findings reveal the GLP/G9a-DNMT module as a mediator of DNA hypermethylation in SPOP-mutated PCa. They suggest that SPOP mutation could be a biomarker for effective treatment of PCa with DNA methylation inhibitor alone or in combination with taxane chemotherapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.