TRANCE IS A NOVEL LIGAND OF THE TUMOR-NECROSIS-FACTOR RECEPTOR FAMILYTHAT ACTIVATES C-JUN N-TERMINAL KINASE IN T-CELLS

A novel member of the tumor necrosis factor (TNF) cytokine family, des ignated TRANCE, was cloned during a search for apoptosis-regulatory ge nes using a somatic cell genetic approach in T cell hybridomas. The TR ANCE 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 th ymus and lymph nodes but not in nonlymphoid tissues and is abundantly expressed in T cells but not in B cells. Cross hybridization of the mo use cDNA to a human thymus library yielded the human homolog, which en codes a protein 83% identical to the mouse ectodomain. Human TRANCE wa s mapped to chromosome 13q14 while mouse TRANCE was located to the por tion of mouse chromosome 14 syntenic with human chromosome 13q14. A re combinant soluble form of TRANCE composed of the entire ectodomain ind uced c-Jun N-terminal kinase (JNK) activation in T cells but not in sp lenic 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.