Inhibition of protein synthesis by the T cell receptor-inducible human TDAG51 gene product.
The T cell death associated gene 51 (TDAG51) was shown to be required for T cell receptor (TCR)-dependent induction of Fas/Apo1/CD95 expression in a murine T cell hybridoma. Despite the absence of a nuclear localization sequence and a nucleic acid binding domain, it was suggested to be localized in the nucleus and to function as a transcription factor regulating Fas-expression. However, we demonstrate that the human (h)TDAG51 protein is localized in the cytoplasm and the nucleoli, suggesting a role in ribosome biogenesis and/or translation regulation. Indeed, it strongly inhibited translation of a luciferase mRNA in a reticulocyte translational extract. Furthermore, cotransfection of hTDAG51 and the luciferase gene into 293T cells resulted in a strong inhibition of luciferase mRNA translation. Our findings were further strengthened by isolating in a yeast two-hybrid screen three proteins which are involved in the regulation of translation. We speculate that hTDAG51 couples TCR signaling to inhibition of protein biosynthesis in activated T lymphocytes.
Hinz
T
T
Department of Immunology, Paul-Ehrlich-Institute, Paul-Ehrlich-Stasse 51-59, D-63225, Langen, Germany. hinth@pei.de
Flindt
S
S
Marx
A
A
Janssen
O
O
Kabelitz
D
D
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002461:Cell Line, Transformed; D002466:Cell Nucleolus / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D066298:In Vitro Techniques; D008156:Luciferases / Q000235:genetics; D008322:Mammals; D010448:Peptide Initiation Factors / Q000235:genetics; D039102:Poly(A)-Binding Proteins; D039665:Prokaryotic Initiation Factor-3; D014176:Protein Biosynthesis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D015003:Yeasts
C491923:PHLDA1 protein, human; D010448:Peptide Initiation Factors; D039102:Poly(A)-Binding Proteins; D039665:Prokaryotic Initiation Factor-3; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D012269:Ribosomal Proteins; D014157:Transcription Factors; C041174:ribosomal protein L14; D008156:Luciferases