TY  - JOUR
A1  - Muthukumar, Yazh
A1  - Münkemer, Johanna
A1  - Mathieu, Daniel
A1  - Richter, Christian
A1  - Schwalbe, Harald
A1  - Steinmetz, Heinrich
A1  - Kessler, Wolfgang
A1  - Reichelt, Joachim
A1  - Beutling, Ulrike
A1  - Frank, Ronald
A1  - Büssow, Konrad
A1  - Heuvel, Joop van den
A1  - Brönstrup, Mark
A1  - Taylor, Richard E.
A1  - Laschat, Sabine
A1  - Sasse, Florenz
T1  - Investigations on the mode of action of gephyronic acid, an inhibitor of eukaryotic protein translation from myxobacteria
T2  - PLoS one
N2  - The 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.
KW  - Protein translation
KW  - Internal ribosome entry site
KW  - Luciferase
KW  - Esters
KW  - Eukaryota
KW  - Translation initiation
KW  - Biotin
KW  - Phosphorylation
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46886
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-468867
SN  - 1932-6203
N1  - This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
VL  - 13
IS  - (7): e0201605
SP  - 1
EP  - 14
PB  - PLoS
CY  - Lawrence, Kan.
ER  -