title: The marine polyketide myriaporone 3/4 stalls translation by targeting the elongation phase.
abstract: 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.
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Yazh
authors.initials: Y
authors.lastname: Muthukumar
authors.forename: Myriam
authors.initials: M
authors.lastname: Roy
authors.forename: Aruna
authors.initials: A
authors.lastname: Raja
authors.forename: Richard E
authors.initials: RE
authors.lastname: Taylor
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002013:Bryozoa / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054736:Elongation Factor 2 Kinase / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D020652:Peptide Elongation Factor 2 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004852:Epoxy Compounds; D020652:Peptide Elongation Factor 2; D011714:Pyrans; C505858:myriaporone 3; D054736:Elongation Factor 2 Kinase