ArticleNature cell biology2016
Nuclear GSK3β promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitylation by USP22.
Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 149 citations in OpenAlex.
- Intestinal epithelial GSK3β governs fumarate-dependent neutrophil reprogramming to promote colorectal cancer.Nature cancer · 2026Article
- FZD5 drives macrophage-mediated immunomodulation and predicts prognosis in glioma: evidence from single-cell sequencing.BMC cancer · 2026Article
- Decoding the Oncogenic Role of USP22 Through Pan-Cancer Genomic and Epigenetic Analysis.Cancer reports (Hoboken, N.J.) · 2026Article
- SAGA/ATAC complexes sustain aberrant chromatin regulation and promote tumorigenesis in diffuse midline glioma.bioRxiv : the preprint server for biology · 2026Article
- CRB2 Activates an Epigenetic Axis to Promote Ferroptosis in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
- Targeting Wnt/β-catenin activation in combination with temozolomide leads to glioblastoma inhibition and long-term survival in mice.Genes & diseases · 2026Article
- Targeting ubiquitin-specific peptidase 22 in solid tumours: from ubiquitination to immunotherapy.Frontiers in cell and developmental biology · 2026Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Phosphorylation enhanced OTUD3 deubiquitination ARID3A promotes the progress of cholangiocarcinoma.Oncogene · 2025Article
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- The multifaceted role of post-translational modifications of LSD1 in cellular processes and disease pathogenesis.Genes & diseases · 2025Review
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- GSK3 acts as a switch for transcriptional programs in a model of low-grade gliomagenesis.Acta neuropathologica communications · 2025Article
- Review
- Histone lysine methylation modifiers controlled by protein stability.Experimental & molecular medicine · 2024Review
- Ubiquitin-specific peptidase 22 controls integrin-dependent cancer cell stemness and metastasis.iScience · 2024Article
- Mature neurons from iPSCs unveil neurodegeneration-related pathways in mucopolysaccharidosis type II: GSK-3β inhibition for therapeutic potential.Cell death & disease · 2024Article
- Strategies that regulate LSD1 for novel therapeutics.Acta pharmaceutica Sinica. B · 2024Review
- Loss of GATA6-mediated up-regulation of UTX promotes pancreatic tumorigenesis and progression.Genes & diseases · 2024Article
- RNF20 contributes to epigenetic immunosuppression through CDK9-dependent LSD1 stabilization.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Emerging evidence has shown that GSK3β plays oncogenic roles in multiple tumour types; however, the underlying mechanisms remain largely unknown. Here, we show that nuclear GSK3β is responsible for the accumulation of the histone demethylase KDM1A and critically regulates histone H3K4 methylation during tumorigenesis. GSK3β phosphorylates KDM1A Ser683 upon priming phosphorylation of KDM1A Ser687 by CK1α. Phosphorylation of KDM1A induces its binding with and deubiquitylation by USP22, leading to KDM1A stabilization. GSK3β- and USP22-dependent KDM1A stabilization is required for the demethylation of histone H3K4, thereby repressing BMP2, CDKN1A and GATA6 transcription, which results in cancer stem cell self-renewal and glioblastoma tumorigenesis. In human glioblastoma specimens, KDM1A levels are correlated with nuclear GSK3β and USP22 levels. Furthermore, a GSK3 inhibitor, tideglusib, sensitizes tumour xenografts to chemotherapy in mice via KDM1A downregulation and improves survival. Our findings demonstrate that nuclear GSK3β- and USP22-mediated KDM1A stabilization is essential for glioblastoma tumorigenesis.
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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.