The Marine Polyketide Myriaporone 3/4 Stalls Translation by Targeting the Elongation Phase. Issue 2 (9th January 2013)

• Record Type: Journal Article
• Authors: Muthukumar, Yazh; Roy, Myriam; Raja, Aruna; Taylor, Richard E.; Sasse, Florenz
• Is Part Of: Chembiochem. Volume 14:Issue 2(2013)
• Page Start: 260
• Page End: 264
• Publication Date: 2013-01-09
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201200522
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>