ArticleOncogene2018
Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The trial behind it
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Activating Cannabinoid receptor 2 alleviates iron overload-induced liver damage via dual modulation of STAT3/hepcidin and Nrf2/FPN1 pathways.Molecular biomedicine · 2026Article
- A proposed convergent molecular chain linking senescence, cancer, and chronic infection to a correctable failure of dendritic cell instruction.Frontiers in immunology · 2026Review
- Unlocking the mitochondrial functional code: unraveling the pathogenesis of ovarian cancer and innovative targets to inhibit malignant behavior.Journal of translational medicine · 2025Review
- Xist condensates: perspectives for therapeutic intervention.Genome biology · 2025Review
- Article
- Enhanced mitochondrial function and delivery from adipose-derived stem cell spheres via the EZH2-H3K27me3-PPARγ pathway for advanced therapy.Stem cell research & therapy · 2025Article
- Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer.Frontiers in pharmacology · 2025Article
- Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential.Molecules (Basel, Switzerland) · 2024Review
- Peripheral Blood DNA Methylation Signatures and Response to Tofacitinib in Moderate-to-severe Ulcerative Colitis.Journal of Crohn's & colitis · 2024Article
- Polycomb repressive complex 2 and its core component EZH2: potential targeted therapeutic strategies for head and neck squamous cell carcinoma.Clinical epigenetics · 2024Review
- Phosphorylation of EZH2 differs HER2-positive breast cancer invasiveness in a site-specific manner.BMC cancer · 2023Article
- Post-Translational Modifications of the DUX4 Protein Impact Toxic Function in FSHD Cell Models.Annals of neurology · 2023Article
- MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Epigenetic modifications in the accumulation and function of myeloid-derived suppressor cells.Frontiers in immunology · 2022Review
- Targeting EZH2-mediated methylation of histone 3 inhibits proliferation of pediatric acute monocytic leukemia cellsCancer biology & therapy · 2021Article
- Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020Review
- Autocrine IL6-Mediated Activation of the STAT3-DNMT Axis Silences the TNFα-RIP1 Necroptosis Pathway to Sustain Survival and Accumulation of Myeloid-Derived Suppressor Cells.Cancer research · 2020Article
- Cyclic AMP Regulates Key Features of Macrophages via PKA: Recruitment, Reprogramming and Efferocytosis.Cells · 2020Article
- EZH2/H3K27Me3 and phosphorylated EZH2 predict chemotherapy response and prognosis in ovarian cancer.PeerJ · 2020Article
- Regulation of E2F1 activity via PKA-mediated phosphorylations.Turkish journal of biology = Turk biyoloji dergisi · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Polycomb repressive complex 2 (PRC2) member enhancer of zeste homolog 2 (EZH2) trimethylates histone H3 lysine 27 (H3K27me3), alters chromatin structure and contributes to epigenetic regulation of gene expression in normal and disease processes. Phosphorylation of EZH2 augmented EZH2 oncogenic activity in cancer but observations have been limited to threonine 350 (T350) and serine 21 (S21) residues by cyclin-dependent kinase 1 and protein kinase B, respectively. In addition, phosphorylation of the evolutionarily conserved T372 motif of EZH2 by p38 resulted in EZH2 interaction with Ying Yang 1 and promoted muscle stem cell differentiation. In the present study, we used epithelial ovarian cancer (OC) cells as a model to demonstrate that phosphorylation of EZH2 at T372 by protein kinase A (PKA) induced a dominant-negative EZH2 phenotype, inhibited OC cell proliferation and migration in vitro and decreased ovarian xenograft tumor growth in vivo. Phosphorylation of T372 by PKA enhanced the interaction between EZH2 and signal transducer and activator of transcription 3 (STAT3), and STAT3 binding to pT372-EZH2 reduced cellular levels of pSTAT3 and downregulated interleukin 6 receptor expression in OC. Furthermore, PKA-mediated pT372-EZH2 decreased ATP levels and altered mitochondrial gene expression, resulting in mitochondrial dysfunction and reduced OC cell growth. These findings demonstrate that PKA-mediated T372 phosphorylation reduces oncogenic EZH2 activity and reveal a novel role for pT372 in regulating EZH2 in OC and possibly other cancers.
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Registered trials
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.