{"doi":"10.1073/pnas.90.3.1023","title":"The c-rel protooncogene product represses NF-kappa B p65-mediated transcriptional activation of the long terminal repeat of type 1 human immunodeficiency virus.","abstract":"<jats:p>The long terminal repeat (LTR) of the type 1 human immunodeficiency virus (HIV-1) and the 5' regulatory region of the gene encoding the interleukin 2 receptor alpha subunit (IL-2R alpha) share functional kappa B enhancer elements involved in the regulation of these inducible transcription units during T-cell activation. These kappa B enhancer elements are recognized by a structurally related family of interactive proteins that includes p50, p65, and the product of the c-rel protooncogene (c-Rel). Recent biochemical studies have shown that p65 and p50 form the prototypical NF-kappa B complex, which is rapidly translocated from the cytoplasm to the nucleus during T-cell activation. This intracellular signaling complex potently stimulates kappa B-directed transcription from either the HIV-1 LTR or the IL-2R alpha promoter via the strong transactivation domain present in p65. We now demonstrate that nuclear expression of human c-Rel, which is induced by either phorbol ester or tumor necrosis factor alpha with delayed kinetics relative to p65, markedly represses p65-mediated activation of these transcription units. These inhibitory effects of c-Rel correlate with its DNA-binding activity but not with its ability to heterodimerize with p50, suggesting that c-Rel inhibition involves competition with p50/p65 for occupancy of the kappa B enhancer element. Together, these findings suggest that one function of c-Rel is as a physiologic repressor of the HIV-1 LTR and IL-2R alpha promoters, serving to efficiently counter the strong transcriptional activating effects of p65.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1993,"id":14663,"datarank":4.2532769159512105,"base_score":4.454347296253507,"endowment":4.454347296253507,"self_citation_contribution":0.6681520944380261,"citation_network_contribution":3.585124821513184,"self_endowment_contribution":0.6681520944380261,"citer_contribution":3.585124821513184,"corpus_percentile":null,"corpus_rank":null,"citation_count":85,"citer_count":78,"citers_with_citation_signal":73,"citers_with_endowment":73,"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":114834,"name":"P Sista","orcid":null,"position":1,"is_corresponding":false},{"id":114836,"name":"S C Sun","orcid":null,"position":2,"is_corresponding":false},{"id":114838,"name":"D W Ballard","orcid":null,"position":3,"is_corresponding":false},{"id":114839,"name":"W C Greene","orcid":null,"position":4,"is_corresponding":false},{"id":114832,"name":"S Doerre","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.454347296253507,"endowment":4.454347296253507,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"8430069","pmcid":null,"openalex_id":"https://openalex.org/W2092489317","authors":[],"funders":[],"total_grants":0,"fwci":5.0412,"citation_percentile":0.96290961,"influential_citations":3,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":1},{"year":2014,"count":1},{"year":2020,"count":2},{"year":2021,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://europepmc.org/articles/pmc45803?pdf=render","host_type":"GREEN"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.90.3.1023","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.90.3.1023","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8430069","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC45803","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/45803","host_type":"repository"}],"fields_of_study":["NF-κB Signaling Pathways","T-cell and Retrovirus Studies","Immune Response and Inflammation","Medicine","Biology","Base Sequence","Chloramphenicol O-Acetyltransferase","DNA Mutational Analysis","Enhancer Elements, Genetic","Gene Expression Regulation, Viral","HIV Long Terminal Repeat","HIV-1","Humans","Interleukin-2","Molecular Sequence Data","NF-kappa B","Promoter Regions, Genetic","Proto-Oncogene Proteins","Proto-Oncogene Proteins c-rel","Repressor Proteins","T-Lymphocytes","Transcription, Genetic","Transfection"],"mesh_terms":["Base Sequence","DNA Mutational Analysis","Enhancer Elements, Genetic","Humans","Interleukin-2","Molecular Sequence Data","Promoter Regions, Genetic","Proto-Oncogene Proteins","Repressor Proteins","T-Lymphocytes","Transcription, Genetic","Transfection","HIV-1","Chloramphenicol O-Acetyltransferase","Gene Expression Regulation, Viral","HIV Long Terminal Repeat","NF-kappa B","Proto-Oncogene Proteins c-rel"],"keywords":["Enhancer","Transactivation","Biology","Long terminal repeat","HIV Long Terminal Repeat","Transcription factor","Repressor","Molecular biology","Promoter","Transcription (linguistics)","Gene","Gene expression","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T13:34:12.282149Z","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":[]}