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/Apol/ CD95 expression in a murine T cell hybridoma. Despite the absence of a nuclear localization sequ ence and a nucleic acid binding domain, it was suggested to be localized in the nucleus and to function as a transcription factor regulating Fas-expre ssion. However, we demonstrate that the human (h)TDAG51 protein is localize d in the cytoplasm and the nucleoli, suggesting a role in ribosome biogenes is 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 f urther strengthened by isolating in a yeast two-hybrid screen three protein s which are involved in the regulation of translation. Pie speculate that h TDAG51 couples TCR signaling to inhibition of protein biosynthesis in activ ated T lymphocytes. (C) 2001 Elsevier Science Inc. All rights reserved.