Woo Jae Kim, Joon Hyun Kim and Sung Key Jang
Department of Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea
To whom correspondence should be addressed
Sung Key Jang, Department of Life Science, Pohang University of Science and Technology, PBC no. 277, San 31, Hyoja-Dong, Pohang 790-784, Republic of Korea. Tel.: +82 54 279 2298; Fax: +82 54 279 8009
Received 20 June 2007; Accepted 17 October 2007; Published online 22 November 2007.
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.
Keywords: eIF4A, 15d-PGJ2, inflammation, proliferation, translation