ArticleCell death & disease2016
DNA-PK-mediated phosphorylation of EZH2 regulates the DNA damage-induced apoptosis to maintain T-cell genomic integrity.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- EZH2 and intracellular CaCellular & molecular immunology · 2026Article
- Integrating network toxicology with multi-omics approaches to elucidate molecular targets and pathway mechanisms in BPA-induced hepatocellular carcinoma.Molecular diversity · 2026Article
- Cancer metabolism in radiation sensitization - complementary roles of O-GlcNAc transferase and PARP1.Journal of cell science · 2026Article
- EZH2 variants derived from cryptic splice sites govern distinct epigenetic patterns during embryonic development.Nucleic acids research · 2025Article
- Inhibiting EZH2 targets atypical teratoid rhabdoid tumor by triggering viral mimicry via both RNA and DNA sensing pathways.Nature communications · 2024Article
- Higher Expression of Ku80 and Ku70 Indicates Hotter Tumor Immune Microenvironment in Hepatocellular Carcinoma and Better CTL-Centered Immunotherapy.Journal of inflammation research · 2024Article
- EZH1/2 dual inhibitors suppress HTLV-1-infected cell proliferation and hyperimmune response in HTLV-1-associated myelopathy.Frontiers in microbiology · 2023Article
- Collateral Victim or Rescue Worker?-The Role of Histone Methyltransferases in DNA Damage Repair and Their Targeting for Therapeutic Opportunities in Cancer.Frontiers in cell and developmental biology · 2021Review
- Inhibition of EZH2 ameliorates bacteria-induced liver injury by repressing RUNX1 in dendritic cells.Cell death & disease · 2020Article
- EZH2 as a Regulator of CD8+ T Cell Fate and Function.Frontiers in immunology · 2020Review
- EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications.Journal of hematology & oncology · 2019Review
- EZH2 upregulation by ERα induces proliferation and migration of papillary thyroid carcinoma.BMC cancer · 2019Article
- Pleiotropic Impact of DNA-PK in Cancer and Implications for Therapeutic Strategies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- The Human T-Cell Leukemia Virus Type 1 Basic Leucine Zipper Factor Attenuates Repair of Double-Stranded DNA Breaks via Nonhomologous End Joining.Journal of virology · 2018Article
- Poly(ADP-ribose) Polymerase 1, PARP1, modifies EZH2 and inhibits EZH2 histone methyltransferase activity after DNA damage.Oncotarget · 2018Article
- Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
EZH2 is a histone methyltransferase whose functions in stem cells and tumor cells are well established. Accumulating evidence shows that EZH2 has critical roles in T cells and could be a promising therapeutic target for several immune diseases. To further reveal the novel functions of EZH2 in human T cells, protein co-immunoprecipitation combined mass spectrometry was conducted and several previous unknown EZH2-interacting proteins were identified. Of them, we focused on a DNA damage responsive protein, Ku80, because of the limited knowledge regarding EZH2 in the DNA damage response. Then, we demonstrated that instead of being methylated by EZH2, Ku80 bridges the interaction between the DNA-dependent protein kinase (DNA-PK) complex and EZH2, thus facilitating EZH2 phosphorylation. Moreover, EZH2 histone methyltransferase activity was enhanced when Ku80 was knocked down or DNA-PK activity was inhibited, suggesting DNA-PK-mediated EZH2 phosphorylation impairs EZH2 histone methyltransferase activity. On the other hand, EZH2 inhibition increased the DNA damage level at the late phase of T-cell activation, suggesting EZH2 involved in genomic integrity maintenance. In conclusion, our study is the first to demonstrate that EZH2 is phosphorylated by the DNA damage responsive complex DNA-PK and regulates DNA damage-mediated T-cell apoptosis, which reveals a novel functional crosstalk between epigenetic regulation and genomic integrity.
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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.