國家衛生研究院 NHRI:Item 3990099045/7041
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    題名: c-Jun-mediated anti-cancer mechanisms of tylophorine
    作者: Yang, CW;Lee, YZ;Hsu, HY;Wu, CM;Chang, HY;Chao, YS;Lee, SJ
    貢獻者: Institute of Biotechnology and Pharmaceutical Research
    摘要: Tylophorine, a phenanthroindolizidine alkaloid, is the major medicinal constituent of herb tylophora indica. Tylophorine treatment increased the accumulation of c-Jun protein, a component of activator protein one (AP1), in carcinoma cells. An in vitro kinase assay revealed that the resultant c-Jun phosphorylation was primarily mediated via activated c-Jun NH(2)-terminal protein kinase (JNK). Moreover, flow cytometry indicated that ectopically overexpressed c-Jun in conjunction with tylophorine significantly increased the number of carcinoma cells that were arrested at the G1 phase. The tylophorine-mediated downregulation of cyclin A2 protein levels is known to be involved in the primary G1 arrest. Chromatin immunoprecipitation and reporter assays revealed that tylophorine enhanced the c-Jun downregulation of the cyclin A2 promoter activity upon increased binding of c-Jun to the deregulation AP1 site and decreased binding to the upregulation ATF site in the cyclin A2 promoter, thereby reducing cyclin A2 expression. Further biochemical studies using pharmacological inhibitors and RNA silencing approaches demonstrated that tylophorine-mediated elevation of the c-Jun protein level occurs primarily via two discrete prolonged signaling pathways: 1) the NF-kappaB/PKCdelta_(MKK4)_JNK cascade, which phosphorylates c-Jun and increases its stability by slowing its ubiquitination, and 2) the PI3K_PDK1_PP2A_eEF2 cascade, which sustains eEF2 activity and thus c-Jun protein translation. To the best of our knowledge, this report is the first to demonstrate the involvement of c-Jun in the anti-cancer activity of tylophorine and the release of c-Jun translation from a global translational blockade via the PI3K_PDK1_eEF2 signaling cascade.
    日期: 2013-06
    關聯: Carcinogenesis. 2013 Jun;34(6):1304-1314.
    Link to: http://dx.doi.org/10.1093/carcin/bgt039
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0143-3334&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000320271100016
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84878970288
    顯示於類別:[李秀珠] 期刊論文
    [趙宇生(2002-2013)] 期刊論文

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