A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis
| Autor: | Carlo Riccardi, Simona Ronchetti, Linda Giunchi, Ludovic Tibor Krausz, Andrea Bartoli, Graziella Migliorati, R. Moraca, Giuseppe Nocentini |
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| Rok vydání: | 1997 |
| Předmět: |
Programmed cell death
Transcription Genetic Ultraviolet Rays T-Lymphocytes T cell Molecular Sequence Data TNF Receptors Nerve Growth Factor Thymus Gland Protein Sorting Signals Biology Transfection Dexamethasone Receptors Tumor Necrosis Factor Mice Glucocorticoid-Induced TNFR-Related Protein medicine Animals Amino Acid Sequence Cloning Molecular Receptor Gene Library Mice Inbred C3H Hybridomas Multidisciplinary Sequence Homology Amino Acid TNFRSF18 T-cell receptor apoptosis Biological Sciences Molecular biology Recombinant Proteins Clone Cells medicine.anatomical_structure Protein Biosynthesis Cancer research Tumor necrosis factor alpha Lymph Nodes Differential display technique Sequence Alignment Spleen |
| Zdroj: | Proceedings of the National Academy of Sciences. 94:6216-6221 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.94.12.6216 |
| Popis: | By comparing untreated and dexamethasone-treated murine T cell hybridoma (3DO) cells by the differential display technique, we have cloned a new gene, GITR (glucocorticoid-induced tumor necrosis factor receptor family-related gene) encoding a new member of the tumor necrosis factor/nerve growth factor receptor family. GITR is a 228-amino acids type I transmembrane protein characterized by three cysteine pseudorepeats in the extracellular domain and similar to CD27 and 4-1BB in the intracellular domain. GITR resulted to be expressed in normal T lymphocytes from thymus, spleen, and lymph nodes, although no expression was detected in other nonlymphoid tissues, including brain, kidney, and liver. Furthermore, GITR expression was induced in T lymphocytes upon activation by anti-CD3 mAb, Con A, or phorbol 12-myristate 13-acetate plus Ca-ionophore treatment. The constitutive expression of a transfected GITR gene induced resistance to anti-CD3 mAb-induced apoptosis, whereas antisense GITR mRNA expression lead to increased sensitivity. The protection toward T cell receptor-induced apoptosis was specific, because other apoptotic signals (Fas triggering, dexamethasone treatment, or UV irradiation) were not modulated by GITR transfection. Thus, GITR is a new member of tumor necrosis factor/nerve growth factor receptor family involved in the regulation of T cell receptor-mediated cell death. |
| Databáze: | OpenAIRE |
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