A New Member of the Tumor Necrosis Factor/Nerve Growth Factor Receptor Family Inhibits T Cell Receptor-Induced Apoptosis

By comparing untreated and dexamethasone-treated murine T cell hybridoma (3DO) cells by the differential display technique, we have cloned a new gene, GITR (glucorticoid-induced tumor necrosis factor receptor family-related gene) encoding a new member of the tumor necrosis factor/nerve growth factor...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1997-06, Vol.94 (12), p.6216-6221
Main Authors: Nocentini, Giuseppe, Giunchi, Linda, Ronchetti, Simona, Krausz, Ludovic Tibor, Bartoli, Andrea, Moraca, Rosalba, Migliorati, Graziella, Riccardi, Carlo
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - radiation effects
Biological Sciences
Cell culture techniques
Cell lines
Cells
Cellular biology
Clone Cells
Cloning
Cloning, Molecular
Complementary DNA
Dexamethasone - pharmacology
Gene Library
Genes
Glucocorticoid-Induced TNFR-Related Protein
Hybridomas
Lymph Nodes - immunology
Messenger RNA
Mice
Mice, Inbred C3H
Molecular Sequence Data
Molecules
Protein Biosynthesis
Protein Sorting Signals - chemistry
Receptors
Receptors, Nerve Growth Factor - biosynthesis
Receptors, Nerve Growth Factor - chemistry
Receptors, Nerve Growth Factor - physiology
Receptors, Tumor Necrosis Factor - biosynthesis
Receptors, Tumor Necrosis Factor - chemistry
Receptors, Tumor Necrosis Factor - physiology
Recombinant Proteins - biosynthesis
Recombinant Proteins - metabolism
Reverse transcriptase polymerase chain reaction
Sequence Alignment
Sequence Homology, Amino Acid
Spleen - immunology
T lymphocytes
T-Lymphocytes - cytology
T-Lymphocytes - immunology
T-Lymphocytes - physiology
Thymus Gland - immunology
Transcription, Genetic
Transfection
Ultraviolet Rays
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Summary:By comparing untreated and dexamethasone-treated murine T cell hybridoma (3DO) cells by the differential display technique, we have cloned a new gene, GITR (glucorticoid-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 Caionophore 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.94.12.6216