Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through inactivation of eIF4A
SCIE
SCOPUS
- Title
- Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through inactivation of eIF4A
- Authors
- Kim, WJ; Kim, JH; Jang, SK
- Date Issued
- 2007-12-12
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- 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.
- Keywords
- eIF4A; 15d-PGJ2; inflammation; proliferation; translation; TRANSFORMATION SUPPRESSOR PDCD4; STRESS GRANULE FORMATION; PRODUCT PATEAMINE-A; KAPPA-B ACTIVATION; RNA HELICASE EIF4A; HEPATITIS-C VIRUS; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); INITIATION CODON; BINDING-PROTEIN; PATHWAY
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/23042
- DOI
- 10.1038/sj.emboj.7601920
- ISSN
- 0261-4189
- Article Type
- Article
- Citation
- EMBO JOURNAL, vol. 26, no. 24, page. 5020 - 5032, 2007-12-12
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