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Anti‐inflammatory lipid mediator 15d‐PGJ2 inhibits translation through inactivation of eIF4A
Author(s) -
Kim Woo Jae,
Kim Joon Hyun,
Jang Sung Key
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601920
Subject(s) - biology , mediator , translation (biology) , microbiology and biotechnology , biochemistry , messenger rna , gene
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 cross‐talk between translation and inflammatory response, and offer new approaches to develop anticancer and anti‐inflammatory drugs that target translation factors including eIF4A.