A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis

• DOI: 10.1073/pnas.94.12.6216
• Publication Date: 2002-07-26T14:31:39Z
• Authors: Giuseppe Nocentini; Linda Giunchi; Simona Ronchetti; Ludovic Tibor Krausz; Andrea Bartoli; Rosalba Moraca; Graziella Migliorati; Carlo Riccardi
• Keywords: 0301 basic medicine; Mice, Inbred C3H; Hybridomas; Sequence Homology, Amino Acid; Molecular Sequence Data; Apoptosis; Receptors, Nerve Growth Factor; Protein Sorting Signals; Dexamethasone; Receptors, Tumor Necrosis Factor; Recombinant Proteins; Clone Cells; 3. Good health; Mice; 03 medical and health sciences; Glucocorticoid-Induced TNFR-Related Protein; Protein Biosynthesis; Animals; Amino Acid Sequence; Lymph Nodes; Cloning, Molecular; Sequence Alignment; TNF; apoptosis; Gene Library

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 member of factor/nerve growth family. is 228-amino acids type I transmembrane protein characterized three cysteine pseudorepeats in extracellular domain similar to CD27 4-1BB intracellular domain. resulted be expressed normal lymphocytes from thymus, spleen, lymph nodes, although no expression was detected other nonlymphoid tissues, including brain, kidney, liver. Furthermore, induced upon activation anti-CD3 mAb, Con A, or phorbol 12-myristate 13-acetate plus Ca-ionophore treatment. The constitutive transfected gene resistance mAb-induced apoptosis, whereas antisense mRNA lead increased sensitivity. protection toward receptor-induced apoptosis specific, because apoptotic signals (Fas triggering, dexamethasone treatment, UV irradiation) were not modulated transfection. Thus, family involved regulation receptor-mediated death.