title: The p53 target gene TRIM22 directly or indirectly interacts with the translation initiation factor eIF4E and inhibits the binding of eIF4E to eIF4G.
abstract: BACKGROUND
  The interferon (IFN)-inducible protein TRIM22 (Staf50) is a member of the tripartite motif protein family and has been suggested a role in the regulation of viral replication as well as of protein ubiquitylation. In addition, we have previously shown that TRIM22 is a direct target gene for the tumour suppressor p53. Consistently, over-expression of TRIM22 inhibits the clonogenic growth of monoblastic U937 cells, suggesting anti-proliferative or cell death-inducing effects.
  
  
  RESULTS
  Here, we demonstrate that TRIM22 directly or indirectly interacts with the eukaryotic translation initiation factor (eIF)4E, and inhibits the binding of eIF4E to eIF4G, thus disturbing the assembly of the eIF4F complex, which is necessary for cap-dependent translation. Furthermore, TRIM22 exerts a repressive effect on luciferase reporter protein levels and to some extent on radiolabelled methionine incorporation. Even though all nuclear mRNAs are capped, some are more dependent on eIF4F than others for translation. The translation of one of these mRNAs, IRF-7C, was indeed found to be repressed in the presence of TRIM22.
  
  
  CONCLUSIONS
  Our data suggest TRIM22 to repress protein translation preferably of some specific mRNAs. Taken together, we show that TRIM22 represses translation by inhibiting the binding of eIF4E to eIF4G, suggesting a mechanism for regulation of protein translation, which may be of importance in response to p53 and/or IFN signalling.
authors.affiliation: Department of Haematology and Transfusion Medicine, BioMedical Centre, Lund University, 221 84 Lund, Sweden. jessica.petersson@gmail.com
authors.forename: Jessica
authors.initials: J
authors.lastname: Petersson
authors.forename: Malin
authors.initials: M
authors.lastname: Ageberg
authors.forename: Carl
authors.initials: C
authors.lastname: Sandén
authors.forename: Tor
authors.initials: T
authors.lastname: Olofsson
authors.forename: Urban
authors.initials: U
authors.lastname: Gullberg
authors.forename: Kristina
authors.initials: K
authors.lastname: Drott
mesh_terms: D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D011485:Protein Binding; D014176:Protein Biosynthesis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D050839:Interferon Regulatory Factor-7; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C495901:TP53 protein, human; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins; D016159:Tumor Suppressor Protein p53; D007372:Interferons