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Sonderforschungsbereich 415:
"Specifity and Pathophysiology of Signal Transduction Pathways"
at Christian-Albrechts-University in Kiel
Project A14: »Role of TDAG51 in cellular activation, proliferation, and apoptosis«
Summary
TDAG51 (T cell death associated gene 51) was originally described as being required for the T cell receptor (TCR)-dependent induction of Fas/CD95 expression in a murine T cell hybridoma. Subsequently, rat and human homologs of murine TDAG51 have been discovered. Overexpression of rat TDAG51 induced Fas-independent apoptosis in neuronal rat cells. Moreover, the human homolog, also called PHLDA1, was identified by a differential RNA display between primary and metastatic melanoma cells.
The aim or our project is to characterize the role of the TCR/CD3-responsive gene TDAG51 for the activation and deactivation (apoptosis) of human T lymphocytes. To this end, Jurkat transfectants with inducible expression of TDAG51 (Tet-on system) have been generated. Inhibitors of various signaling pathways are used to investigate the role of protein kinases and MAP kinases in the TCR-dependent induction of TDAG51 in non-transformed primary and clonal human T cell populations. Furthermore, the significance of the constitutive expression of TDAG51 in pancreatic and other epithelial tumor cells as opposed to the inducible expression in T lymphocytes is investigated.
Original papers
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Oberg, H.H., Sipos, B., Kalthoff, H., Janssen, O., Kabelitz, D. (2004)
 Expression of the human TDAG51 gene is regulated by MAP kinase via PKC and/or Ras and does not correlate with AICD. |
| Cell Death Differ, in press |
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Qian, J., Linkermann, A., Schulze-Osthoff, K., Wajant, H., Kabelitz, D. Janssen, O. (2004)
FasL-induced interference with TCR/CD3 stimulation of human peripheral blood lymphocytes |
| Cell Death Differ, submitted |
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Ghadimi, M.P., Sanzenbacher, R., Thiede, B., Wenzel, J., Jing, Q., Plomann, M., Borkhardt, A., Kabelitz, D., Janssen, O. (2002)
Identification of interaction partners of the cytosolic polyproline region of CD95 ligand (CD178). |
| FEBS Lett 519: 50-58 |
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Ussat, S., Werner, U.-E., Kruse, M.-L., Lüschen, S., Scherer, G., Kabelitz, D., und Adam-Klages, S. (2002)
Upregulation of p21WAF1/Cip1 precedes tumor necrosis factor-induced necrosis-like cell death. |
| Biochem. Biophys. Res. Commun. 294, 672-679 |
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Hinz, T., Flindt, S., Marx, A., Janssen, O., Kabelitz, D. (2001)
Inhibition of protein synthesis by the T cell receptor-inducible human TDAG51 gene product. |
| Cell Signal 13: 345-352. |
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Wenzel, J., Sanzenbacher, R., Ghadimi, M., Lewitzky, M., Zhou, Q., Kaplan, D., Kabelitz, D., Feller, S.M., Janssen, O. (2001)
Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor. |
| FEBS Letters 509: 255-262. |
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Reviews
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Janssen, O., Qian, J., Linkermann, A., Kabelitz, D. (2003)
CD95 ligand - death factor and costimulatory molecule? |
| Cell Death Diff,. 10, 1215-1225 |
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Linkermann, A., Qian, J., Kabelitz, D., Janssen, O. (2003)
FasL as a death regulator and signal transducer. |
| Signal Transduction 3, 33-46 |
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Adam, D., Heinrich, M., Kabelitz, D., Schütze, S. (2002)
Ceramide: does it matter for T cells? |
| Trends Immunol 23: 1-4 |
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