Inhibition of eukaryotic translation initiation by the marine natural product pateamine A

Woon Kai Low, Yongjun Dang, Tilman Schneider-Poetsch, Zonggao Shi, Nam Song Choi, William C. Merrick, Daniel Romo, Jun O. Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Translation initiation in eukaryotes is accomplished through the coordinated and orderly action of a large number of proteins, including the eIF4 initiation factors. Herein, we report that pateamine A (PatA), a potent antiproliferative and proapoptotic marine natural product, inhibits cap-dependent eukaryotic translation initiation. PatA bound to and enhanced the intrinsic enzymatic activities of eIF4A, yet it inhibited eIF4A-eIF4G association and promoted the formation of a stable ternary complex between eIF4A and eIF4B. These changes in eIF4A affinity for its partner proteins upon binding to PatA caused the stalling of initiation complexes on mRNA in vitro and induced stress granule formation in vivo. These results suggest that PatA will be a valuable molecular probe for future studies of eukaryotic translation initiation and may serve as a lead compound for the development of anticancer agents.

Original languageEnglish (US)
Pages (from-to)709-722
Number of pages14
JournalMolecular cell
Volume20
Issue number5
DOIs
StatePublished - Dec 9 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Inhibition of eukaryotic translation initiation by the marine natural product pateamine A'. Together they form a unique fingerprint.

Cite this