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Wong, BR, Rho, J, Arron, J, Robinson, E, Orlinick, J, Chao, M, Kalachikov, S, Cayani, E, Bartlett, FS 3rd, Frankel, WN, Lee, SY and Choi, Y (1997) TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J. Biol. Chem. 272:25190-4


A novel member of the tumor necrosis factor (TNF) cytokine family, designated TRANCE, was cloned during a search for apoptosis-regulatory genes using a somatic cell genetic approach in T cell hybridomas. The TRANCE gene encodes a type II membrane protein of 316 amino acids with a predicted molecular mass of 35 kDa. Its extracellular domain is most closely related to TRAIL, FasL, and TNF. TRANCE is an immediate early gene up-regulated by TCR stimulation and is controlled by calcineurin-regulated transcription factors. TRANCE is most highly expressed in thymus and lymph nodes but not in nonlymphoid tissues and is abundantly expressed in T cells but not in B cells. Cross-hybridization of the mouse cDNA to a human thymus library yielded the human homolog, which encodes a protein 83% identical to the mouse ectodomain. Human TRANCE was mapped to chromosome 13q14 while mouse TRANCE was located to the portion of mouse chromosome 14 syntenic with human chromosome 13q14. A recombinant soluble form of TRANCE composed of the entire ectodomain induced c-Jun N-terminal kinase (JNK) activation in T cells but not in splenic B cells or in bone marrow-derived dendritic cells. These results suggest a role for this TNF-related ligand in the regulation of the T cell-dependent immune response.




Amino Acid Sequence; Animals; Apoptosis; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Carrier Proteins; Cell Line; Chromosome Mapping; Chromosomes, Human, Pair 13; Cloning, Molecular; Cycloheximide/pharmacology; Enzyme Activation; Genes, Immediate-Early; Humans; JNK Mitogen-Activated Protein Kinases; Ligands; Membrane Glycoproteins/genetics; Membrane Glycoproteins/metabolism; Membrane Proteins/chemistry; Mice; Mitogen-Activated Protein Kinases; Molecular Sequence Data; Organ Specificity; Polymerase Chain Reaction; Protein Biosynthesis/drug effects; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Tumor Necrosis Factor/metabolism; Receptors, Tumor Necrosis Factor/physiology; Recombinant Proteins/biosynthesis; Recombinant Proteins/chemistry; Recombinant Proteins/metabolism; Sequence Alignment; Sequence Homology, Amino Acid; T-Lymphocytes; Tacrolimus/pharmacology; Thymus Gland/metabolism