TRANCE Is a Novel Ligand of the Tumor Necrosis Factor Receptor Family That Activates c-Jun N-terminal Kinase in T Cells*
- Brian R. Wong‡,
- Jaerang Rho‡,§,
- Joseph Arron‡,
- Elizabeth Robinson‡,§,
- Jason Orlinick¶,
- Moses Chao¶,
- Sergey Kalachikov‖,
- Eftihia Cayani‖,
- Frederick S. Bartlett III**,
- Wayne N. Frankel**,
- Soo Young Lee‡ and
- Yongwon Choi‡,§‡
- From the §Howard Hughes Medical Institute, ‡The Rockefeller University, New York, New York 10021, the ¶Department of Cell Biology and Anatomy, Hematology/Oncology Division, Cornell University Medical College, New York, New York 10021, **The Jackson Laboratory, Bar Harbor, Maine 04609, and ‖Columbia Genome Center, College of Physicians and Surgeons of Columbia University, New York, New York 10032
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. HumanTRANCE was mapped to chromosome 13q14 while mouseTRANCE 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.
Footnotes
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↵* This work was supported in part by a Klingenstein fellowship (to W. N. F.), National Institutes of Health Medical Scientist Training Program Grant GM07739 (to B. R. W), and National Institutes of Health Grants NS3336 (to W. N. F.), CA56490 (to M. C.), and CA525133 (to Y. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Assistant investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed: Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., New York, NY 10021. Tel.: 212-327-7441; Fax: 212-327-7319; E-mail:choi{at}rockvax.rockefeller.edu.
- Received July 24, 1997.
