Abstract 3085: The IFN inducible p53 target gene TRIM22 binds to the translation initation factor eIF4E and represses translation through disturbing the assembly of the eIF4F complex

Abstract

Abstract TRIM22 (Staf50) is an interferon (IFN)-inducible protein as well as a p53 target gene. It belongs to the TRIM (TRIpartite Motif) family proteins, characterized of a conserved tripartite motif consisting of a RING finger, B-box and a coiled-coil domain. The TRIM family includes more than 70 proteins, involved in various biological processes; e.g. apoptosis and cell proliferation. Consistently, several TRIM family members are involved in cancer. TRIM22 has been suggested to be an antiviral protein, capable of restricting HIV-, hepatitis B- and encephalomyocarditis replication. The molecular mechanisms for TRIM22 are unclear, but the antiviral activity may be dependent on the ubiquitylation capacity of TRIM22. We have previously shown it to suppress the clonogenic growth of leukemic U-937 cells, suggesting anti-proliferative or cell death-inducing effects. Now, we demonstrate that TRIM22 binds to the translation initiation factor eIF4E, and inhibits the binding of eIF4E to eIF4G, thus disturbing the assembly of the eIF4F complex, vital for cap dependent translation of mRNA. As a consequence, TRIM22 represses translation, as shown by decreased reporter protein levels, as well as global protein synthesis. Pulse-chase and cycloheximide experiments reveal that the repressive effects on the reporter protein is not due to increased protein degradation. Taken together, our data show TRIM22 to repress the binding of eIF4E to eIF4G, suggesting a novel translation regulating mechanism, possibly mediated in response to p53 and/or IFN signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3085. doi:10.1158/1538-7445.AM2011-3085