Evidence for a role of a tumor necrosis factor-α (TNF-α)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival Journal Article


Authors: Lum, L.; Wong, B. R.; Josien, R.; Becherer, J. D.; Erdjument-Bromage, H.; Schlöndorff, J.; Tempst, P.; Choi, Y.; Blobel, C. P.
Article Title: Evidence for a role of a tumor necrosis factor-α (TNF-α)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival
Abstract: Tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE), a member of the TNF family, is a dendritic cell survival factor and is essential for osteoclastogenesis and osteoclast activation. In this report we demonstrate (i) that TRANCE, like TNF-α, is made as a membrane-anchored precursor, which is released from the plasma membrane by a metalloprotease; (ii) that soluble TRANCE has potent dendritic cell survival and osteoclastogenic activity; (iii) that the metalloprotease-disintegrin TNF-α convertase (TACE) can cleave immunoprecipitated TRANCE in vitro in a fashion that mimics the cleavage observed in tissue culture cells; and (iv) that in vitro cleavage of a TRANCE ectodomain/CD8 fusion protein and of a peptide corresponding to the TRANCE cleavage site by TACE occurs at the same site that is used when TRANCE is shed from cells into the supernatant. We propose that the TRANCE ectodomain is released from cells by TACE or a related metalloprotease-disintegrin, and that this release is an important component of the function of TRANCE in bone and immune homeostasis.
Keywords: controlled study; nonhuman; animal cell; animals; cell survival; dendritic cell; cell line; cell differentiation; cos cells; immunoregulation; cytokine; dendritic cells; amino acid sequence; tumor necrosis factor alpha; membrane glycoproteins; carrier proteins; protein secretion; osteoclast; osteoclasts; hydrolysis; adam proteins; rank ligand; bone metabolism; receptor activator of nuclear factor-kappa b; metalloendopeptidases; humans; priority journal; article
Journal Title: Journal of Biological Chemistry
Volume: 274
Issue: 19
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 1999-05-07
Start Page: 13613
End Page: 13618
Language: English
DOI: 10.1074/jbc.274.19.13613
PUBMED: 10224132
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
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MSK Authors
  1. Carl Blobel
    52 Blobel
  2. Lawrence Lum
    10 Lum
  3. Paul J Tempst
    311 Tempst