https://scholars.lib.ntu.edu.tw/handle/123456789/160016
標題: | HCMV IE2-mediated inhibition of HAT activity downregulates p53 function | 作者: | Wang, Y.H. Lee, S.C. Hsu, C.H. Chang, Margaret DT Tai, K.Y. Yang, Y.T. Wang, P.S. Chen, C.J. Wu, C.We. Juan, L.J. |
關鍵字: | IE2;HAT;HCMV;p53 | 公開日期: | 2004 | 出版社: | Taipei:National Taiwan University Department of Molecular Medicine | 起(迄)頁: | - | 來源出版物: | The EMBO Journal 23, 2269–2280 | 摘要: | Targeting of cellular histone acetyltransferases (HATs) by viral proteins is important in the development of virusassociated diseases. The immediate-early 2 protein (IE2) of human cytomegalovirus (HCMV) binds to the tumor suppressor, p53, and inactivates its functions by unknown mechanisms. Here, we show that IE2 binds to the HAT domain of the p53 coactivators, p300 and CREB-binding protein (CBP), and blocks their acetyltransferase activity on both histones and p53. The minimal HAT inactivation region on IE2 involves the N-terminal 98 amino acids. The in vivo DNA binding of p53 and local histone acetylation on p53-dependent promoters are all reduced by IE2, but not by mutant IE2 proteins that lack the HAT inhibition region. Furthermore, the p53 acetylation site mutant, K320/373/382R, retains both DNA binding and promoter transactivation activity in vivo and these effects are repressed by IE2 as well. Together with the finding that only wild-type IE2 exerts an antiapoptotic effect, our results suggest that HCMV IE2 downregulates p53-dependent gene activation by inhibiting p300/CBP-mediated local histone acetylation and that IE2 may have oncogenic activity. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/2006111501221915 | 其他識別: | 246246/2006111501221915 |
顯示於: | 分子醫學研究所 |
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