TRANCE Is a Novel Ligand of the Tumor Necrosis Factor Receptor Family That Activates c-Jun N-terminal Kinase in T Cells

作者：Brian R. Wong, Jaerang Rho, Joseph R. Arron, Elizabeth A. Robinson, Jason R. Orlinick, Moses V. Chao, Sergey M. Kalachikov, Eftihia Cayani, Frederick S. Bartlett, Wayne N. Frankel, Soo Young Lee, Yongwon Choi · 发表于：Journal of Biological Chemistry · 年份：1997 · DOI：10.1074/jbc.272.40.25190 · 被引用次数：1062 · 研究领域：Immune Response and Inflammation、NF-κB Signaling Pathways、Immune Cell Function and Interaction

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.