Role of Tumor Suppressor p53 in HDAC Inhibitor-induced Epstein-Barr Virus Reactivation

• Main Authors: Yow-Chang Lo, 羅宥璋
• Other Authors: 蔡錦華
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/62175668514962617371

碩士 === 臺灣大學 === 微生物學研究所 === 95 === It was reported that p53 accumulates in some EBV-infected tissue cells, meanwhile, high titer antibodies against EBV lytic products were also observed in those patients’ sera, suggesting p53 may play a role in EBV reactivation. Here, we show that RNA interference of p53 in NA cells, an NPC cell line infected with Akata EBV, blocks HDAC inhibitor-induced EBV reactivation. Both transcripts and promoter activity of the EBV immediately early gene Zta are no longer induced by HDAC inhibitor in the absence of p53 expression. p53 may regulate EBV reactivation through Zta promoter. However, EMSA and DAPA experiments demonstrate that p53 does not bind to Zta promoter. EMSA experiments are also conducted to compare factors binding to ZIA/B、ZIC、ZII、ZIIIA and ZV in the absence or presence of p53. Knocking down of p53 results in augmentation of ZIA/B complex2. ZIA/B complex2 formation is through the middle region of ZIA/B probe. However, Zp-reporter assay demonstrates that mutation of the complex2-binding site does not alter HDAC inhibitor-induced Zta promoter activity. Post-translational modification of p53 by HDAC inhibitor may play a role during EBV reactivation. Phosphorylation of p53-Ser46 increases during TSA time course treatment. However, phosphorylation of p53-Ser46 is not important for HDAC inhibitor-induced EBV reactivation. Intriguingly, HDAC inhibitor-induced EBV reactivation is abolished upon ectopically expression of a mutant p53 ( 248m ) in H1299A cel line, suggesting that p53 DNA binding ability is required for HDAC inhibitor-induced EBV reactivation. We conclude that p53 acts as an important regulator of Zta promoter in the process of HDAC inhibitor-induced EBV reactivation, and it provides a novel role for p53 in virus-host interaction.