國家衛生研究院 NHRI:Item 3990099045/3298
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    题名: Amantadine as a regulator of internal ribosome entry site
    作者: Chen, YJ;Zeng, SJ;Hsu, JT;Horng, JT;Yang, HM;Shih, SR;Chu, YT;Wu, TY
    贡献者: Division of Biotechnology and Pharmaceutical Research
    摘要: Aim: Studies of eukaryotes have yielded 2 translation initiation mechanisms: a classical cap-dependent mechanism and a cap-independent mechanism proceeding through the internal ribosomal entry site (IRES). We hypothesized that it might be possible to identify compounds that may distinguish between cap-dependent translation and cap-independent IRES-mediated translation. Methods: To facilitate compound screening, we developed bicistronic reporter constructs containing a ?-galactosidase gene (?-gal) and a secreted human placental alkaline phosphatase (SEAP) reporter gene. Following transcription, the ?-gal gene is translated by a cap-dependent mechanism, while SEAP expression is controlled by the IRES derived from either enterovirus 71 (EV-71) or encephalomyocardi-tis virus (EMCV). This assay could potentially identify compounds that inhibit SEAP expression (cap-independent) without affecting ?-gal activity (cap-dependent). Results: Using a bicistronic plasmid-based transient transfection assay in the COS-1 cells, we identified amantadine, a compound that inhibited the IRES of EV71- and EMCV-mediated cap-independent translation but did not interfere with cap-dependent translation when the dose of amantadine was lower than 0.25 mg/mL. Conclusion: These results imply that amantadine may distinguish between cap-dependent translation and cap-independent IRES-mediated translation and can be used to regulate gene expression at a translational level. ?2008 CPS and SIMM.
    日期: 2008-11
    關聯: Acta Pharmacologica Sinica. 2008 Nov;29(11):1327-1333.
    Link to: http://dx.doi.org/10.1111/j.1745-7254.2008.00876.x
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1671-4083&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000260527300007
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=55149088381
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