title: Differential regulation of translation and eIF4E phosphorylation during human thymocyte maturation.
abstract: Activation of peripheral blood T cells by cross-linking of CD3 results in a rapid and substantial rise in translation rates and proliferation, which coincides with an increase in the cap-binding protein, eIF4E activity. In contrast, immature CD4+ CD8+ double-positive (DP) thymocytes undergo apoptosis in response to anti-CD3 mAb. We have investigated translation initiation in the response of immature thymocytes to activating signals. Activation by anti-CD3 + anti-CD4 of immature CD4+ CD8+ DP thymocytes results in a rapid decrease in protein synthesis. In contrast, similar treatment of CD4+ or CD8+ single-positive (SP) thymocytes results in an increase in protein synthesis. The rate of protein synthesis is linked to the phosphorylation status of eIF4E. Following anti-CD3 + anti-CD4 stimulation, eIF4E phosphorylation strongly decreases in immature DP thymocytes, whereas it increases in mature SP thymocytes. The expression of 4E-BP2, a specific repressor of eIF4E function, is high in DP cells but decreases during maturation, raising the possibility of a role for 4E-BP2 in repressing eIF4E phosphorylation. These data provide evidence for differential regulation of the translational machinery during T cell development.
authors.affiliation: INSERM U.365, Institut Curie, Paris, France. lberetta@curie.fr
authors.forename: L
authors.initials: L
authors.lastname: Beretta
authors.forename: N G
authors.initials: NG
authors.lastname: Singer
authors.forename: R
authors.initials: R
authors.lastname: Hinderer
authors.forename: A C
authors.initials: AC
authors.lastname: Gingras
authors.forename: B
authors.initials: B
authors.lastname: Richardson
authors.forename: S M
authors.initials: SM
authors.lastname: Hanash
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000096:biosynthesis; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002675:Child, Preschool; D003432:Cross-Linking Reagents; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D006801:Humans; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000096:biosynthesis; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; C087000:EIF4EBP1 protein, human; C104151:EIF4EBP2 protein, human; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell