{"corpus_id":46114137,"paper_sha":"00141090385e8c0341c6fd85c1ceadc18452a0ca","doi":"10.4049/jimmunol.156.7.2465","arxiv_id":null,"pmid":8786306,"pmcid":null,"mag_id":2119878533,"dblp_id":null,"acl_id":null,"title":"Functional analysis of the lymphotoxin-beta promoter. Sequence requirements for PMA activation.","year":1996,"publication_date":"1996-04-01","venue":"Journal of Immunology","journal":{"name":"Journal of immunology","pages":"\n          2465-72\n        ","volume":"156 7"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":0,"citation_count":38,"influential_citation_count":1,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Base Sequence","mj":false,"ui":"D001483"},{"d":"Binding Sites","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D001665"},{"d":"Cell Line","mj":false,"ui":"D002460"},{"d":"Cycloheximide","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D003513"},{"d":"DNA","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D004247"},{"d":"DNA Probes","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D015342"},{"d":"Gene Expression Regulation","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D005786"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Lymphotoxin-alpha","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D008233"},{"d":"Lymphotoxin-beta","mj":false,"ui":"D053308"},{"d":"Membrane Proteins","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D008565"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Molecular Sequence Data","mj":false,"ui":"D008969"},{"d":"Promoter Regions, Genetic","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D011401"},{"d":"Protein Binding","mj":false,"ui":"D011485"},{"d":"RNA, Messenger","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D012333"},{"d":"Sequence Deletion","mj":false,"ui":"D017384"},{"d":"Tetradecanoylphorbol Acetate","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D013755"},{"d":"Transcription Factors","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D014157"}],"chemicals":[{"n":"DNA Probes","ui":"D015342","reg":"0"},{"n":"LTB protein, human","ui":"C505886","reg":"0"},{"n":"Ltb protein, mouse","ui":"C505887","reg":"0"},{"n":"Lymphotoxin-alpha","ui":"D008233","reg":"0"},{"n":"Lymphotoxin-beta","ui":"D053308","reg":"0"},{"n":"Membrane Proteins","ui":"D008565","reg":"0"},{"n":"RNA, Messenger","ui":"D012333","reg":"0"},{"n":"Transcription Factors","ui":"D014157","reg":"0"},{"n":"DNA","ui":"D004247","reg":"9007-49-2"},{"n":"Cycloheximide","ui":"D003513","reg":"98600C0908"},{"n":"Tetradecanoylphorbol Acetate","ui":"D013755","reg":"NI40JAQ945"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://journals.aai.org/jimmunol/article-pdf/156/7/2465/1072327/2465.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/00141090385e8c0341c6fd85c1ceadc18452a0ca","s2_open_access_license":null,"s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Membrane lymphotoxin (LT) complex is a trimer composed of two subunits , LT-alpha and LT-beta of which the latter is a 33-kDa transmembrane protein. The LT-beta gene is expressed in lymphoid cells and organs, but little is known about its inducible regulation. Previously, the surface expression of LT-beta in Jurkat cells has been shown to increase in response to PMA. In this report, we used this model to study the transcriptional control of the human and murine LT-beta genes. PMA strongly induced the expression of LT-beta mRNA, and the level of induction was not changed markedly by cycloheximide (CHX) treatment. The LT-beta promoter region contains conserved Egr-1, nuclear factor (NF)-kappaB, and Ets binding sites, and PMA-inducible factors bound to these sites were detected by the gel-retardation technique (electrophoretic mobility shift assay (EMSA)). To identify sequences involved in transcriptional control, sets of human and mouse promoter-chloramphenicol acetyltransferase (CAT) constructs were generated and assayed by transient transfections. The PMA response was lost after deletion of the distal Ets binding site at -110. Mutations at either the Ets or NF-kappaB sites that prevented factor binding dramatically reduced PMA-inducible promoter activity, suggesting cooperative interaction between corresponding transcription factors in PMA activation. Mutation at the Egr-1 site also resulted in substantial loss of promoter activity, and the residual activity may be attributed to binding of constitutively expressed Sp-1 to the same site. We propose that the interaction between the members of NF-kappaB and Ets families of transcription factors and their cognate sites in the promoter is the major determinant of inducible expression of the LT-beta gene in Jurkat cells.","claims":[{"public_id":"cl_b89458d9da4b2407fabf4e9e799c7c21","status":"active","text":"Deletion of the distal Ets binding site at -110 abolished the PMA response in promoter-CAT constructs.","confidence":0.95,"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale 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(322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"}],"url":"https://sah.borca.ai/claims/cl_3f9ac5cb40de8d6252bcbba82864fd9c"},{"public_id":"cl_c956763a3f5cdf8b7bfcc32c34f427c5","status":"active","text":"Mutations at either the Ets or NF-kappaB sites that prevent factor binding dramatically reduced PMA-inducible promoter activity, suggesting cooperative interaction between corresponding transcription factors.","confidence":0.9,"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"}],"url":"https://sah.borca.ai/claims/cl_c956763a3f5cdf8b7bfcc32c34f427c5"},{"public_id":"cl_8c2f763a09739729b9a1ffbb6542261d","status":"active","text":"PMA strongly induced LT-beta mRNA expression in Jurkat cells, and this induction was not markedly changed by cycloheximide treatment.","confidence":0.9,"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"}],"url":"https://sah.borca.ai/claims/cl_8c2f763a09739729b9a1ffbb6542261d"},{"public_id":"cl_602c21f1bbe0d9b47aee719fdbc16b19","status":"active","text":"The PMA-inducible promoter activity of LT-beta depends on conserved Egr-1, NF-kappaB, and Ets binding sites in the promoter region.","confidence":0.9,"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["extraction"],"url":"https://sah.borca.ai/u/ezd9qvkvax"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"}],"url":"https://sah.borca.ai/claims/cl_602c21f1bbe0d9b47aee719fdbc16b19"}],"concepts":[{"public_id":"co_0d323a02a368c8fa713dead18f82b79b","status":"active","name":"LT-beta gene","description":"Gene encoding lymphotoxin beta, a 33-kDa transmembrane protein expressed in lymphoid cells.","types":["gene"],"aliases":["lymphotoxin-beta gene"],"contributors":[{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ 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