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BMRF1 has been previously shown to activate transcription of an EBV early promoter, BHLF1, though a GC-rich motif which binds to SP1 and ZBP-89, although the exact mechanism for this effect is not known (D. J. Law, S. A. Tarle, and J. L. Merchant, Mamm. Genome 9:165-167, 1998). Here we demonstrate that BMRF1 activates transcription of the cellular gastrin gene in telomerase-immortalized keratinocytes. Furthermore, BMRF1 activated a reporter gene construct driven by the gastrin promoter in a variety of cell types, and this effect was mediated by two SP1\/ZBP-89 binding sites in the gastrin promoter. ZBP-89 has been previously shown to negatively regulate the gastrin promoter. However, ZBP-89 can function as either a negative or positive regulator of transcription, depending upon the promoter and perhaps other, as-yet-unidentified factors. BMRF1 increased the binding of ZBP-89 to the gastrin promoter, and a ZBP-89-GAL4 fusion protein was converted into a positive transcriptional regulator by cotransfection with BMRF1. BMRF1 also enhanced the transcriptional activity of an SP1-GAL4 fusion protein. These results suggest that BMRF1 activates target promoters through its effect on both the SP1 and ZBP-89 transcription factors. Furthermore, as the EBV genome is present in up to 10% of gastric cancers, and the different forms of gastrin are growth factors for gastrointestinal epithelium, our results suggest a mechanism by which lytic EBV infection could promote the growth of gastric cells.<\/jats:p>","DOI":"10.1128\/jvi.79.2.745-755.2005","type":"journal-article","created":{"date-parts":[[2004,12,21]],"date-time":"2004-12-21T03:05:49Z","timestamp":1103598349000},"page":"745-755","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["The Epstein-Barr Virus Protein BMRF1 Activates Gastrin Transcription"],"prefix":"10.1128","volume":"79","author":[{"given":"Elizabeth A.","family":"Holley-Guthrie","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Seaman","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasanna","family":"Bhende","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanita L.","family":"Merchant","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon C.","family":"Kenney","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center"},{"name":"Department of Medicine"},{"name":"Department of Immunology and Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004249200"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg929"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.21.6095"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1443"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi992298f"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.278.4.C697"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(92)90280-K"},{"key":"e_1_3_2_9_2","first-page":"315","volume":"518","year":"1999","unstructured":"Dockray, G. 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