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

被引：206

作者：

Low, WK

Dang, YJ

Schneider-Poetsch, T

Shi, ZG

Choi, NS

Merrick, WC

Romo, D ^{[1
]}

Liu, JO

机构：

[1] Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA

[2] Johns Hopkins Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA

[3] Johns Hopkins Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[4] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[5] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA

来源：

MOLECULAR CELL | 2005年 / 20卷 / 05期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1016/j.molcel.2005.10.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 anti proliferative 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.

引用

页码：709 / 722

页数：14

共 48 条

[1] A SACCHAROMYCES-CEREVISIAE HOMOLOG OF MAMMALIAN TRANSLATION INITIATION FACTOR-4B CONTRIBUTES TO RNA HELICASE ACTIVITY [J].