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The Marine Polyketide Myriaporone 3/4 Stalls Translation by Targeting the Elongation Phase
Author(s) -
Muthukumar Yazh,
Roy Myriam,
Raja Aruna,
Taylor Richard E.,
Sasse Florenz
Publication year - 2013
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201200522
Subject(s) - polyketide , elongation , translation (biology) , chemistry , nanotechnology , stereochemistry , biochemistry , materials science , biosynthesis , gene , messenger rna , metallurgy , ultimate tensile strength
Myriaporone 3/4, a cytotoxic polyketide, has been reported as an inhibitor of eukaryotic protein synthesis. However, the mechanism by which it inhibits translation was unknown. Here we show that myriaporone 3/4 stalls protein synthesis in the elongation phase by inducing phosphorylation of eukaryotic elongation factor 2. The phosphorylation results from direct binding of myriaporone 3/4 to eukaryotic elongation factor 2 kinase. Our study also shows that myriaporone 3/4 in the nanomolar range inhibits in vitro tube formation by endothelial cells without being cytotoxic. In general, myriaporone 3/4 was at least 300 times less toxic to primary cells than to tumor cells.