Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through inactivation of eIF4A

被引：88

作者：

Kim, Woo Jae ^{[1
]}

Kim, Joon Hyun ^{[1
]}

Jang, Sung Key ^{[1
]}

机构：

[1] Pohang Univ Sci & Technol, Dept Life Sci, Pohang, South Korea

来源：

EMBO JOURNAL | 2007年 / 26卷 / 24期

关键词：

eIF4A; 15d-PGJ2; inflammation; proliferation; translation;

D O I：

10.1038/sj.emboj.7601920

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：

The signaling lipid molecule 15-deoxy-delta 12,14-prostaglandin J2 (15d-PGJ2) has multiple cellular functions, including anti-inflammatory and antineoplastic activities. Here, we report that 15d-PGJ2 blocks translation through inactivation of translational initiation factor eIF4A. Binding of 15d-PGJ2 to eIF4A blocks the interaction between eIF4A and eIF4G that is essential for translation of many mRNAs. Cysteine 264 in eIF4A is the target site of 15d-PGJ2. The antineoplastic activity of 15d-PGJ2 is likely attributed to inhibition of translation. Moreover, inhibition of translation by 15d-PGJ2 results in stress granule (SG) formation, into which TRAF2 is sequestered. The sequestration of TRAF2 contributes to the anti-inflammatory activity of 15d-PGJ2. These findings reveal a novel crosstalk between translation and inflammatory response, and offer new approaches to develop anticancer and anti-inflammatory drugs that target translation factors including eIF4A.

引用

页码：5020 / 5032

页数：13

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