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The growth program of infected B cells is initiated and maintained by the viral transcription factor EBV nuclear antigen 2 (EBNA2), which regulates viral and cellular genes, including the proto-oncogene c-<jats:italic>myc<\/jats:italic>. In our study, patterns of protein expression in B cells with and without EBNA2 were analyzed by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. For this purpose, we used a conditional immortalization system for EBV, a B cell line (EREB2-5) that expresses an estrogen receptor-EBNA2 fusion protein. In order to discriminate downstream targets of c-Myc from c-Myc-independent EBNA2 targets, we used an EREB2-5-derived cell line, P493-6, in which c-Myc is expressed under the control of a tetracycline-regulated promoter. Of 20 identified EBNA2 target proteins, 11 were c-Myc dependent and therefore most probably associated with proliferation, and one of these proteins was a posttranslationally modified protein, i.e., hypusinylated eIF5a. Finally, to estimate the relevance of EBNA2 targets during early EBV infection, we analyzed the proteomes of primary B cells before and after infection with EBV. The protein expression pattern induced upon EBV infection was similar to that following EBNA2 activation. These findings underscore the value of EREB2-5 cells as an appropriate model system for the analysis of early events in the process of EBV-mediated B-cell immortalization.<\/jats:p>","DOI":"10.1128\/jvi.78.8.3941-3952.2004","type":"journal-article","created":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T18:33:15Z","timestamp":1080325995000},"page":"3941-3952","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":51,"title":["Identification of Epstein-Barr Virus (EBV) Nuclear Antigen 2 (EBNA2) Target Proteins by Proteome Analysis: Activation of EBNA2 in Conditionally Immortalized B Cells Reflects Early Events after Infection of Primary B Cells by EBV"],"prefix":"10.1128","volume":"78","author":[{"given":"Martin","family":"Schlee","sequence":"first","affiliation":[{"name":"Institute of Clinical Molecular Biology and Tumor Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Krug","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, Ludwig-Maximilians University of Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Gires","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Group \u201cMolecular Oncology,\u201d GSF-Research Center for Health and Environment, and Department of Head and Neck Surgery, Ludwig-Maximilians University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Zeidler","sequence":"additional","affiliation":[{"name":"Vaecgene Biotech Inc., D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hammerschmidt","sequence":"additional","affiliation":[{"name":"Department of Gene Vectors, GSF-National Research Center for EnvironmentHealth"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Mailhammer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology and Tumor Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Laux","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology and Tumor Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Sauer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology and Tumor Genetics"},{"name":"Department for Biomolecular Sciences, University of Manchester Institute for Science and Technology, The Mill, M60 1QD Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josip","family":"Lovric","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology and Tumor Genetics"},{"name":"Department for Biomolecular Sciences, University of Manchester Institute for Science and Technology, The Mill, M60 1QD Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg W.","family":"Bornkamm","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology and Tumor Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00175-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(97)00222-4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00049-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/mp.52.6.307"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.16.7804"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5257.1858"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.4.2209-2220.1993"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/elps.11501401209"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150080203"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2000.0781"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2525"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007260170050"},{"key":"e_1_3_2_14_2","first-page":"2298","volume":"8","year":"2002","unstructured":"Chen, G., T. 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