{"doi":"10.1128/mcb.10.8.3965","title":"The cytokine response element of the rat alpha 1-acid glycoprotein gene is a complex of several interacting regulatory sequences.","abstract":"<jats:p>Expression of the rat alpha 1-acid glycoprotein gene is stimulated by interleukin-1 (IL-1) and interleukin-6 (IL-6) and is synergistically enhanced by the combination of the two. The distal regulatory element (DRE), a 142-base-pair (bp) sequence located 5 kilobase pairs upstream of the transcriptional start site, appears to be crucial for this cytokine response. The cytokine-specific regulatory sequences within the DRE have been identified by inserting individual DRE subregions, selected combinations of these, or a few linker mutated fragments into a plasmid containing an enhancerless simian virus 40 promoter linked to the chloramphenicol acetyltransferase gene. The regulatory activity was determined in transiently transfected human and rat hepatoma cells. The IL-1 response region was confined to the 5'-most 62 bp of the DRE, and its function seemed to depend on at least two separate components. The same region was also responsive to phorbol ester treatment. The IL-6 regulatory function was dependent on a 54-bp sequence located within the 3' half of the DRE. When the IL-1 response region was recombined with the IL-6 regulatory region of the DRE or with IL-6 response elements of other plasma protein genes, a strong cooperative action by IL-1 and IL-6 was achieved. The functional DRE sequences were recognized by nuclear proteins extracted from rat liver and hepatoma cells. However, no cytokine-inducible binding activity was detectable, which suggests that transcriptional regulation through the DRE might be controlled by posttranslational modification of constitutively bound trans-acting factors.</jats:p>","journal":"Molecular and Cellular Biology","year":1990,"id":20951,"datarank":5.006237567378883,"base_score":4.465908118654584,"endowment":4.465908118654584,"self_citation_contribution":0.6698862177981877,"citation_network_contribution":4.336351349580696,"self_endowment_contribution":0.6698862177981877,"citer_contribution":4.336351349580696,"corpus_percentile":null,"corpus_rank":null,"citation_count":86,"citer_count":76,"citers_with_citation_signal":72,"citers_with_endowment":72,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":136725,"name":"H Baumann","orcid":null,"position":1,"is_corresponding":false},{"id":136724,"name":"K A Won","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.465908118654584,"endowment":4.465908118654584,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"2196441","pmcid":null,"openalex_id":"https://openalex.org/W2042012480","authors":[],"funders":[],"total_grants":0,"fwci":4.3426,"citation_percentile":0.95114429,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2015,"count":1},{"year":2019,"count":1},{"year":2020,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/360907","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/360907","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1128/MCB.10.8.3965","host_type":"publisher"},{"url":"https://doi.org/10.1128/mcb.10.8.3965","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/2196441","host_type":"repository"}],"fields_of_study":["Immune Response and Inflammation","Cytokine Signaling Pathways and Interactions","interferon and immune responses"],"mesh_terms":["Animals","Base Sequence","Biological Factors","Cell Line","DNA-Binding Proteins","Gene Expression Regulation","Genes","Humans","Interleukin-1","Liver","Liver Neoplasms, Experimental","Molecular Sequence Data","Orosomucoid","Plasmids","Recombinant Proteins","Regulatory Sequences, Nucleic Acid","Sequence Homology, Nucleic Acid","Transfection","Interleukin-6","Cytokines","Rats"],"keywords":["Biology","Chloramphenicol acetyltransferase","Regulatory sequence","Molecular biology","Transfection","Gene","Regulation of gene expression","Cytokine","Peptide sequence","Negative regulatory element","Cell biology","Promoter","Gene expression","Biochemistry","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T13:48:12.506802Z","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":[]}