Anti‐inflammatory lipid mediator 15d‐PGJ2 inhibits translation through inactivation of eIF4A
Copyright policy )Anti‐inflammatory lipid mediator 15d‐PGJ2 inhibits translation through inactivation of eIF4A
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.
- Pohang University of Science and Technology Korea (Republic of)
Arsenites, proliferation, TRANSFORMATION SUPPRESSOR PDCD4, Emetine, Eukaryotic Initiation Factor-2, Anti-Inflammatory Agents, translation, 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2), Cyclopentanes, HEPATITIS-C VIRUS, Cytoplasmic Granules, Poly(A)-Binding Proteins, PRODUCT PATEAMINE-A, Dinoprostone, KAPPA-B ACTIVATION, PATHWAY, STRESS GRANULE FORMATION, Humans, Hypoglycemic Agents, Chromans, Enzyme Inhibitors, Inflammation, Prostaglandins A, Arachidonic Acid, Prostaglandin D2, 15d-PGJ2, PPAR gamma, BINDING-PROTEIN, INITIATION CODON, Gene Expression Regulation, inflammation, Eukaryotic Initiation Factor-4A, RNA HELICASE EIF4A, eIF4A, HeLa Cells
Arsenites, proliferation, TRANSFORMATION SUPPRESSOR PDCD4, Emetine, Eukaryotic Initiation Factor-2, Anti-Inflammatory Agents, translation, 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2), Cyclopentanes, HEPATITIS-C VIRUS, Cytoplasmic Granules, Poly(A)-Binding Proteins, PRODUCT PATEAMINE-A, Dinoprostone, KAPPA-B ACTIVATION, PATHWAY, STRESS GRANULE FORMATION, Humans, Hypoglycemic Agents, Chromans, Enzyme Inhibitors, Inflammation, Prostaglandins A, Arachidonic Acid, Prostaglandin D2, 15d-PGJ2, PPAR gamma, BINDING-PROTEIN, INITIATION CODON, Gene Expression Regulation, inflammation, Eukaryotic Initiation Factor-4A, RNA HELICASE EIF4A, eIF4A, HeLa Cells
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