HCMV IE2-mediated inhibition of HAT activity downregulates p53 function

Chih Hung Hsu, Margaret D.T. Chang, Kang Yu Tai, Yu Ting Yang, Pei Shan Wang, Chi Ju Chen, Yan Hsiung Wang, Sheng Chung Lee, Cheng-Wen Wu, Li Jung Juan*

*此作品的通信作者

研究成果: Article同行評審

64 引文 斯高帕斯(Scopus)

摘要

Targeting of cellular histone acetyltransferases (HATs) by viral proteins is important in the development of virus-associated 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.

原文English
頁(從 - 到)2269-2280
頁數12
期刊EMBO Journal
23
發行號11
DOIs
出版狀態Published - 2 六月 2004

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