{"doi":"10.17615/ate4-p887","title":"Regulation of ENT1 expression and ENT1-dependent nucleoside transport by c-Jun N-terminal kinase","abstract":"Equilibrative Nucleoside Transporters (ENTs) are facilitative transporters broadly selective for pyrimidine and purine nucleosides and are essential for the modulation of nucleoside concentration and nucleoside analog availability. Resistance to nucleoside-derived drugs strongly correlates with a deficiency of ENT1 expression in several tumor cells. Thus, it is crucial to understand the mechanisms by which this transporter is modulated. Using a mouse myeloid leukemic cell line as a model, we investigated whether stress-activated kinases regulate ENT1 expression and function. JNK activation, but not p38 MAPK results in rapid loss of mENT1 function, mRNA expression and promoter activity. c-Jun but not the mutant c-Jun Ser63/73Ala, decreased mENT1 promoter activity. Moreover cJun bound to an AP-1 site identified at −1196 of the promoter, suggesting a specific role for this transcription factor in mENT1 regulation. We propose that activation of JNK-cJun pathway negatively regulates mENT1 and suggest that this mechanism might contribute to the development of nucleoside analog-derived drug resistance.","journal":"UNC Libraries","year":2020,"id":135209,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":592530,"name":"Shannon Z. Jones","orcid":null,"position":1,"is_corresponding":false},{"id":591943,"name":"Jing Yang","orcid":"0000-0003-2799-0000","position":2,"is_corresponding":false},{"id":412458,"name":"Eric I. Zimmerman","orcid":null,"position":3,"is_corresponding":false},{"id":456700,"name":"Min Huang","orcid":"0000-0002-2844-5680","position":4,"is_corresponding":false},{"id":592531,"name":"Andrea V. Leisewitz","orcid":null,"position":5,"is_corresponding":false},{"id":397772,"name":"Lee M. Graves","orcid":"0000-0002-4736-9855","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:31.787520Z","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":[]}