{"doi":"10.1016/j.jbc.2021.101209","title":"DNA-PKcs kinase activity stabilizes the transcription factor Egr1 in activated immune cells","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 of and and of DNA-PKcs a DNA-PKcs of of serine to protein and transcription of in T Our identify DNA-PKcs a critical T cell activation and T cell and a in Egr1 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 of and and of DNA-PKcs a DNA-PKcs of of serine to protein and transcription of in T Our identify DNA-PKcs a critical T cell activation and T cell and a in Egr1 function for DNA-dependent protein kinase catalytic subunit DNA-PKcs is in the and repair of DNA nonhomologous end joining (NHEJ). However, kinase of function in DNA-PKcs a in and and T cell in a repair DNA for repair of DNA of the catalytic subunit of the in and DNA-PKcs in primarily to the function of DNA-PKcs in is for and in immune cells in is in and DNA-PKcs in T DNA-dependent protein kinase in and and function a function for DNA-PKcs in the immune that is yet to cells a of the immune response T cell and a of to of T cells in and that T cell is critical for the of to T T cell activation that T cell and end is the activation of transcription that of and the and T cell of the transcription factor in T cells T cell a cell of transcription and T cells is that DNA-PKcs T cell immune cells, of transcription factor T cells, DNA-PKcs of both and a of and DNA-dependent protein kinase in and and function cells to DNA-dependent protein Our that DNA-PKcs also of the subunit of in T cells, and of DNA-PKcs of DNA-PKcs that DNA DNA-PKcs activation of the immune response the transcription factor and its into the to is a DNA for indicate that DNA-PKcs a role in the of to the of DNA-PKcs the of to the and of DNA-PKcs in T we that DNA-PKcs also of the early response Egr1 (early growth response a transcription factor critical for is in T of early growth response is for the of cells to and and growth response the Egr1 within of to transcription of for immune cell function activation and early response in and of early response factor and of kinase of transcription and its a transcription factor in the the of targeting to T cell immunity and for T cells response the of Egr1 to a phosphorylation of DNA-PKcs. of DNA-PKcs of serine of Egr1 in of Egr1 protein to of of early Egr1 that DNA-PKcs a critical and transcription of T cell is DNA-PKcs of T the of in DNA-PKcs is we to identify DNA-PKcs phosphorylation targets in T cell To we performed a quantitative screen for T cells and and and a kinase of DNA-PKcs of a DNA-dependent protein kinase of DNA-PKcs of break of quantitative for a quantitative and of phosph","journal":"Journal of Biological Chemistry","year":2021,"id":176733,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":719527,"name":"Lyle Burdine","orcid":"0000-0002-5892-2281","position":1,"is_corresponding":false},{"id":719528,"name":"David K. Harrison","orcid":"0000-0003-1068-7611","position":2,"is_corresponding":false},{"id":532240,"name":"Ana Clara P. Azevedo‐Pouly","orcid":"0000-0001-8308-9271","position":3,"is_corresponding":false},{"id":245937,"name":"Aaron J. Storey","orcid":"0000-0003-4089-5008","position":4,"is_corresponding":false},{"id":720111,"name":"Olivia G. Moffett","orcid":null,"position":5,"is_corresponding":false},{"id":342237,"name":"Samuel G. Mackintosh","orcid":"0000-0002-5530-8403","position":6,"is_corresponding":false},{"id":720112,"name":"Marie Burdine","orcid":null,"position":7,"is_corresponding":false},{"id":719526,"name":"Zachary J. Waldrip","orcid":"0000-0002-4210-8832","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:47:23.605867Z","pmid":"34562454","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}