{"doi":"10.1101/2021.06.04.446996","title":"DNA-PKcs kinase activity stabilizes the transcription factor Egr1 in activated immune cells","abstract":"Abstract DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known primarily for its function in DNA double-stranded break repair and non-homologous 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 first order phosphorylation targets of DNA-PKcs. Results indicate that DNA-PKcs phosphorylates the transcription factor Egr1 (early growth response protein 1) at S301. Expression of Egr1 is induced early upon T cell activation and dictates T cell response by modulating expression of cytokines and key costimulatory molecules. Mutation of serine 301 to alanine via CRISPR-Cas9 resulted in increased proteasomal degradation of Egr1 and a decrease in Egr1-dependent transcription of IL2 (interleukin-2) 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220896,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"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":32,"raw_metadata":null,"created_at":"2026-07-18T23:53:50.838581Z","pmid":null,"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":[]}