ArticleThe Journal of biological chemistry2021
DNA-PKcs kinase activity stabilizes the transcription factor Egr1 in activated immune cells.
Article in The Journal of biological chemistry, 2021. 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, 21 citations in OpenAlex.
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- DNA-PKcs controls the cytotoxic T cell response to cancer and transplant allograft through regulating LAT-dependent signaling.Cell reports · 2026Article
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 2025Review
- DNA-PKcs-Driven YAP1 Phosphorylation and Nuclear Translocation: a Key Regulator of Ferroptosis in Hyperglycemia-Induced Cardiac Dysfunction in Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DNA-PKcs, a player winding and dancing with RNA metabolism and diseases.Cellular & molecular biology letters · 2025Review
- Discovery of the DNA-PKcs inhibitor DA-143 which exhibits enhanced solubility relative to NU7441.Scientific reports · 2024Article
- The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.EMBO reports · 2024Article
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- Epidermal growth factor augments the self-renewal capacity of aged hematopoietic stem cells.iScience · 2024Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- Comparative analysis of basal and etoposide-induced alterations in gene expression by DNA-PKcs kinase activity.Frontiers in genetics · 2024Article
- Article
- Chemical inhibition of DNA-PKcs impairs the activation and cytotoxicity of CD4Immunology and cell biology · 2023Article
- DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs): Beyond the DNA Double-Strand Break Repair.Molecules and cells · 2023Review
- Phosphoproteomic Approaches for Identifying Phosphatase and Kinase Substrates.Molecules (Basel, Switzerland) · 2023Review
- The combination of SMRT sequencing and Illumina sequencing highlights organ-specific and age-specific expression patterns of miRNAs in Sika Deer.Frontiers in veterinary science · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known primarily for its function in DNA double-stranded break repair and nonhomologous end joining (NHEJ). However, DNA-PKcs also has a critical yet undefined role in immunity impacting both myeloid and lymphoid cell lineages spurring interest in targeting DNA-PKcs for therapeutic strategies in immune-related diseases. To gain insight into the function of DNA-PKcs within immune cells, we performed a quantitative phosphoproteomic screen in T cells to identify phosphorylation targets of DNA-PKcs. Our results indicate that DNA-PKcs phosphorylates the transcription factor Egr1 (early growth response protein 1) at serine 301. Expression of Egr1 is induced early upon T cell activation and dictates T cell response by modulating expression of cytokines and key costimulatory molecules such as IL (interleukin) 2, IL6, IFNγ, and NFκB. Inhibition of DNA-PKcs by treatment with a DNA-PKcs specific inhibitor NU7441 or shRNA knockdown increased proteasomal degradation of Egr1. Mutation of serine 301 to alanine via CRISPR-Cas9 reduced EGR1 protein expression and decreased Egr1-dependent transcription of IL2 in activated T cells. Our findings identify DNA-PKcs as a critical intermediary link between T cell activation and T cell fate and a novel phosphosite involved in regulating Egr1 activity.
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Registered trials
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