The role of p53 in EBV infection - Down-regulation of EBV transcription mediated by EBNA2 and EBNALP by p53 is implicated in cell protection from EBV infection
碩士 === 慈濟大學 === 生命科學研究所 === 97 === Transcriptions of specific viral promoters and cellular genes driven by Epstein-Barr Virus (EBV) nuclear antigen 2 (EBNA2) and leader protein (LP) are essential for immortalization of B lymphocytes upon EBV infection. In particular, EBNA2 acts as a transcription ac...
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ndltd-TW-097TCU051050062015-10-13T12:04:55Z http://ndltd.ncl.edu.tw/handle/09774113002702003040 The role of p53 in EBV infection - Down-regulation of EBV transcription mediated by EBNA2 and EBNALP by p53 is implicated in cell protection from EBV infection p53抑制由EB病毒核抗原2和前導蛋白所主導EB病毒潛伏基因轉錄作用的分子機制探討 Yi-li Min 閔譯立 碩士 慈濟大學 生命科學研究所 97 Transcriptions of specific viral promoters and cellular genes driven by Epstein-Barr Virus (EBV) nuclear antigen 2 (EBNA2) and leader protein (LP) are essential for immortalization of B lymphocytes upon EBV infection. In particular, EBNA2 acts as a transcription activator, whereas EBNALP augments the transcription mediated by EBNA2. The interactions of EBNALP and p53, and p53 and EBNA2 were further emphasized in this study. We hypothesize that p53 may contribute in cell defense to EBV infection via modulation of viral promoter activities induced by EBNA2 and EBNALP although such a specific event is likely suppressed by the gene products of EBV. To test this possibility, several cell lines derived from EBV associated diseases were analyzed for the protein expression levels of p53. Among all three types of EBV latency infected cells, the expression levels of p53 were extremely low or barely detectable in the EBV infected cells in comparison with the phenotypes of EBV negative cells. We next investigated whether over-expression of p53 could affect the LMP1 promoter-luciferase reporter (LMP1-Luc) induced by the EBNA2 and EBNALP in non-EBV infected BJAB cells or the protein expression of LMP1 resulted from the endogenous EBV genome induced by EBNA2 and EBNALP in EBV latency I infected AKATA lymphoblasts. Our results revealed that ectopically expressed p53 strongly down-regulates LMP1-Luc reporter activated by EBNA2 and EBNALP. We found both the 64PXXP67 of activation domain (AD) and the oligomerization (Olg) domain of p53 trigger the robust repressing effects on LMP1-Luc activities activated by EBNA2, whereas proline rich (Pro) and Olg domains were specifically implicated in down-regulation of EBNALP co-activation with EBNA2. Furthermore, our results also suggested that the modes by which down-regulation of EBNA2 or EBNALP by p53 are mechanistically different. Interestingly, we found p53 can down-regulate EBNALP co-activation with EBNA2 but not with p300/CBP, suggesting a selective down-regulation of EBNALP by p53 may depend on the co-activating targets of EBNALP. Our current hypothesis is that p53 likely recruits the co-repressor mSin3A to EBV promoters via binding to EBNA2 and EBNALP. Taken together, we demonstrate a novel strategy employed by p53 to modulate cell protection from EBV infection through down-regulation of EBNA2 and EBNALP mediated transcription. Chih-wen Peng 彭致文 學位論文 ; thesis 38 en_US |
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碩士 === 慈濟大學 === 生命科學研究所 === 97 === Transcriptions of specific viral promoters and cellular genes driven by Epstein-Barr Virus (EBV) nuclear antigen 2 (EBNA2) and leader protein (LP) are essential for immortalization of B lymphocytes upon EBV infection. In particular, EBNA2 acts as a transcription activator, whereas EBNALP augments the transcription mediated by EBNA2. The interactions of EBNALP and p53, and p53 and EBNA2 were further emphasized in this study. We hypothesize that p53 may contribute in cell defense to EBV infection via modulation of viral promoter activities induced by EBNA2 and EBNALP although such a specific event is likely suppressed by the gene products of EBV. To test this possibility, several cell lines derived from EBV associated diseases were analyzed for the protein expression levels of p53. Among all three types of EBV latency infected cells, the expression levels of p53 were extremely low or barely detectable in the EBV infected cells in comparison with the phenotypes of EBV negative cells. We next investigated whether over-expression of p53 could affect the LMP1 promoter-luciferase reporter (LMP1-Luc) induced by the EBNA2 and EBNALP in non-EBV infected BJAB cells or the protein expression of LMP1 resulted from the endogenous EBV genome induced by EBNA2 and EBNALP in EBV latency I infected AKATA lymphoblasts. Our results revealed that ectopically expressed p53 strongly down-regulates LMP1-Luc reporter activated by EBNA2 and EBNALP. We found both the 64PXXP67 of activation domain (AD) and the oligomerization (Olg) domain of p53 trigger the robust repressing effects on LMP1-Luc activities activated by EBNA2, whereas proline rich (Pro) and Olg domains were specifically implicated in down-regulation of EBNALP co-activation with EBNA2. Furthermore, our results also suggested that the modes by which down-regulation of EBNA2 or EBNALP by p53 are mechanistically different. Interestingly, we found p53 can down-regulate EBNALP co-activation with EBNA2 but not with p300/CBP, suggesting a selective down-regulation of EBNALP by p53 may depend on the co-activating targets of EBNALP. Our current hypothesis is that p53 likely recruits the co-repressor mSin3A to EBV promoters via binding to EBNA2 and EBNALP. Taken together, we demonstrate a novel strategy employed by p53 to modulate cell protection from EBV infection through down-regulation of EBNA2 and EBNALP mediated transcription.
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author2 |
Chih-wen Peng |
author_facet |
Chih-wen Peng Yi-li Min 閔譯立 |
author |
Yi-li Min 閔譯立 |
spellingShingle |
Yi-li Min 閔譯立 The role of p53 in EBV infection - Down-regulation of EBV transcription mediated by EBNA2 and EBNALP by p53 is implicated in cell protection from EBV infection |
author_sort |
Yi-li Min |
title |
The role of p53 in EBV infection - Down-regulation of EBV transcription mediated by EBNA2 and EBNALP by p53 is implicated in cell protection from EBV infection |
title_short |
The role of p53 in EBV infection - Down-regulation of EBV transcription mediated by EBNA2 and EBNALP by p53 is implicated in cell protection from EBV infection |
title_full |
The role of p53 in EBV infection - Down-regulation of EBV transcription mediated by EBNA2 and EBNALP by p53 is implicated in cell protection from EBV infection |
title_fullStr |
The role of p53 in EBV infection - Down-regulation of EBV transcription mediated by EBNA2 and EBNALP by p53 is implicated in cell protection from EBV infection |
title_full_unstemmed |
The role of p53 in EBV infection - Down-regulation of EBV transcription mediated by EBNA2 and EBNALP by p53 is implicated in cell protection from EBV infection |
title_sort |
role of p53 in ebv infection - down-regulation of ebv transcription mediated by ebna2 and ebnalp by p53 is implicated in cell protection from ebv infection |
url |
http://ndltd.ncl.edu.tw/handle/09774113002702003040 |
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