| Summary: | 碩士 === 國立臺灣大學 === 微生物學研究所 === 87 === In Epstein-Barr virus (EBV) latently infected cells, EBNA-1 proteins could bind to the specific DNA sequences as a homodimer form in order to promote viral DNA replication and to maintain the viral DNA as an episomal form. Both lines of evidence that EBNA-1 protein was only viral protein existed in most EBV-associated malignancies and that EBNA-1 could induce B lymphoma in transgenic mice model, indicated that EBNA-1 might play some roles in the carcinogenesis of EBV-associated tumors. However, it is still not clear what cellular factors would be involved or regulated in this EBNA-1-mediated pathway. The major goal of this thesis was to investigate whatever cellular molecules regulated or activated by EBNA-1 using EBNA-1-expression stable clone and transient transfection assay system.
In the preliminary results, it was observed that EBNA-1 could enhance the phosphorylation of p38 protein and increase the expression of Egr-1 in both stable and transient EBNA-1-expression RHEK-1 and 293 cells. Furthermore, the induction of Egr-1 protein by EBNA-1 could be suppressed by SB202190, a specific inhibitor for p38 phosphorylation. Both data suggested that EBNA-1 could stimulate the synthesis of Egr-1 protein through the action of phosphorylation of p38.
It has been reported that NF-κB is one of the downstream molecule of p38 protein. According to the analysis in our luciferase activity assay, the activity of NF-κB could be increased at a dose-dependent manner by the presence of EBNA-1 proteins in the transfection assay. However, it still needs more experiments to prove whether this induction of NF-κB by EBNA-1 is mediated through p38 or not.
We had found that the EBNA-1-expression RHEK-1 cells were grown better than the control RHEK-1 cells, in low serum culture condition. Here, the results of luciferase activity assay showed that both AP-1 and CRE activity were higher in the EBNA-1 expression cells at the low serum culture condition. We hypothesize that EBNA-1 could promote the cell growth under the low serum circumstance.
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