Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through inactivation of eIF4A
Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through inactivation of eIF4A
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DOI：
10.1038/sj.emboj.7601920
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发表时间：
2007-12-12
期刊：
影响因子：
11.4
通讯作者：
Jang, Sung Key
中科院分区：
文献类型：
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作者：
Kim, Woo Jae;Kim, Joon Hyun;Jang, Sung Key
信号脂质分子15-脱氧- 12,14-前列腺素J2 （15d-PGJ2）具有多种细胞功能，包括抗炎和抗肿瘤活性。在这里，我们报道了15d-PGJ2通过灭活翻译起始因子eIF4A来阻断翻译。15d-PGJ2与eIF4A的结合阻断了eIF4A和eIF4G之间的相互作用，而eIF4A和eIF4G对于许多mrna的翻译至关重要。eIF4A中的半胱氨酸264是15d-PGJ2的靶点。15d-PGJ2的抗肿瘤活性可能归因于抑制翻译。此外，15d-PGJ2对翻译的抑制导致应激颗粒（SG）的形成，TRAF2被隔离在其中。TRAF2的隔离有助于15d-PGJ2的抗炎活性。这些发现揭示了翻译和炎症反应之间的一种新的串扰，并为开发针对包括eIF4A在内的翻译因子的抗癌和抗炎药物提供了新的途径。
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.