國家衛生研究院 NHRI:Item 3990099045/2692
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2692


    Title: HCMV IE2-mediated inhibition of HAT activity downregulates p53 function
    Authors: Hsu, CH;Chang, MDT;Tai, KY;Yang, YT;Wang, PS;Chen, CJ;Wang, YH;Lee, SC;Wu, CW;Juan, LJ
    Contributors: National Institute of Cancer Research
    Abstract: 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.
    Keywords: Biochemistry & Molecular Biology;Cell Biology
    Date: 2004-06-02
    Relation: EMBO Journal. 2004 Jun;23(11):2269-2280.
    Link to: http://dx.doi.org/10.1038/sj.emboj.7600239
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0261-4189&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000222333400009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=3042600724
    Appears in Collections:[Li-Jung Juan(2000-2006)] Periodical Articles
    [Cheng-Wen Wu(1996-2008)] Periodical Articles

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