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dc.contributor.authorMuthukumar, Yazh
dc.contributor.authorMünkemer, Johanna
dc.contributor.authorMathieu, Daniel
dc.contributor.authorRichter, Christian
dc.contributor.authorSchwalbe, Harald
dc.contributor.authorSteinmetz, Heinrich
dc.contributor.authorKessler, Wolfgang
dc.contributor.authorReichelt, Joachim
dc.contributor.authorBeutling, Ulrike
dc.contributor.authorFrank, Ronald
dc.contributor.authorBüssow, Konrad
dc.contributor.authorvan den Heuvel, Joop
dc.contributor.authorBrönstrup, Mark
dc.contributor.authorTaylor, Richard E
dc.contributor.authorLASCHAT, SABINE
dc.contributor.authorSasse, Florenz
dc.date.accessioned2019-01-07T14:43:20Z
dc.date.available2019-01-07T14:43:20Z
dc.date.issued2018-01-01
dc.identifier.citationPLoS One. 2018 Jul 31;13(7):e0201605. doi: 10.1371/journal.pone.0201605 eCollection 2018.en_US
dc.identifier.issn1932-6203
dc.identifier.pmid30063768
dc.identifier.doi10.1371/journal.pone.0201605
dc.identifier.urihttp://hdl.handle.net/10033/621634
dc.description.abstractThe identification of inhibitors of eukaryotic protein biosynthesis, which are targeting single translation factors, is highly demanded. Here we report on a small molecule inhibitor, gephyronic acid, isolated from the myxobacterium Archangium gephyra that inhibits growth of transformed mammalian cell lines in the nM range. In direct comparison, primary human fibroblasts were shown to be less sensitive to toxic effects of gephyronic acid than cancer-derived cells. Gephyronic acid is targeting the protein translation system. Experiments with IRES dual luciferase reporter assays identified it as an inhibitor of the translation initiation. DARTs approaches, co-localization studies and pull-down assays indicate that the binding partner could be the eukaryotic initiation factor 2 subunit alpha (eIF2α). Gephyronic acid seems to have a different mode of action than the structurally related polyketides tedanolide, myriaporone, and pederin and is a valuable tool for investigating the eukaryotic translation system. Because cancer derived cells were found to be especially sensitive, gephyronic acid could potentially find use as a drug candidate.en_US
dc.publisherPLOSen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleInvestigations on the mode of action of gephyronic acid, an inhibitor of eukaryotic protein translation from myxobacteria.en_US
dc.typeArticleen_US
dc.identifier.journalPLOSOneen_US
refterms.dateFOA2019-01-07T14:43:20Z
dc.source.journaltitlePloS one


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