Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Carrier Proteins*
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Cell Line
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Chromosome Mapping
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Chromosomes, Human, Pair 13
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Cloning, Molecular
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Cycloheximide / pharmacology
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Enzyme Activation
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Genes, Immediate-Early
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Humans
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JNK Mitogen-Activated Protein Kinases
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Ligands
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism*
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Membrane Proteins / chemistry*
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Mice
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Organ Specificity
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Polymerase Chain Reaction
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Protein Biosynthesis / drug effects
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor / physiology*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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T-Lymphocytes
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Tacrolimus / pharmacology
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Thymus Gland / metabolism
Substances
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Carrier Proteins
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Ligands
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Membrane Glycoproteins
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Membrane Proteins
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins
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TNFRSF11A protein, human
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TNFSF11 protein, human
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Tnfrsf11a protein, mouse
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Tnfsf11 protein, mouse
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Cycloheximide
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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Tacrolimus
Associated data
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GENBANK/AF013170
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GENBANK/AF013171