A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells

  title={A metalloproteinase disintegrin that releases tumour-necrosis factor-$\alpha$ from cells},
  author={Roy A. Black and Charles T. Rauch and Carl J. Kozlosky and Jacques J. Peschon and Jennifer L. Slack and Martin F. Wolfson and Beverly J. Castner and Kim L. Stocking and Pranitha Reddy and Subhashini Srinivasan and Nicole Nelson and Norman Boiani and Kenneth Schooley and Mary J. Gerhart and Raymond Davis and Jeffrey N. Fitzner and Richard S. Johnson and Raymond J. Paxton and Carl J. March and Douglas Pat Cerretti},
Mammalian cells proteolytically release (shed) the extracellular domains of many cell-surface proteins1. Modification of the cell surface in this way can alter the cell's responsiveness to its environment2 and release potent soluble regulatory factors3. The release of soluble tumour-necrosis factor-α (TNF-α) from its membrane-bound precursor4,5 is one of the most intensively studied shedding events because this inflammatory cytokine is so physiologically important6,7. The inhibition of TNF… 
Pro-Tumor Necrosis Factor-α Processing Activity Is Tightly Controlled by a Component That Does Not Affect Notch Processing*
Biochemical evidence shows that the component that controls TACE is different from protein kinase C, the only known activator of protein ectodomain shedding, and that this component does not affect biosynthesis or processing of TACE or other metalloprotease disintegrins.
Involvement of a disintegrin and metalloproteinase 10 and 17 in shedding of tumor necrosis factor-alpha.
Both ADAM10 and ADAM17 can be a TNF-alpha sheddase and that their significance could be determined by their expression levels and the abundance of tissue inhibitor of metalloproteinases.
The ADAM metalloproteinases
Inhibition of the Metalloproteinase Domain of Mouse TACE
Preliminary results suggest that TACE is not involved in the degradation of the ECM proteins tested and does not indirectly participate in ECM degradation by activating MMP-2 or M MP-9.
Functional Analysis of the Domain Structure of Tumor Necrosis Factor-α Converting Enzyme*
It is found that TACE must be expressed with its membrane-anchoring domain for phorbol ester-stimulated shedding of TNF, p75 TNFR, and IL-1R-II, but that the cytoplasmic domain is not required for the shedding of these substrates.
Proteasome inhibition activates the transport and the ectodomain shedding of TNF-α receptors in human endothelial cells
Evidence is provided that proteasome inhibitors increase TACE-dependent TNFR-shedding in endothelial cells, supporting the use of these molecules in inflammatory disorders and enhancing the sensitivity to the proapoptotic effect of recombinant TNF-α.
Processing of tumor necrosis factor by the membrane-bound TNF-alpha-converting enzyme, but not its truncated soluble form.
It is suggested that binding of the membrane-anchored but not the soluble form of TACE to TNF-alpha results in efficient ectodomain shedding, and that FasL secretase is a metalloproteinase similar, but not identical, to TACE.
Tumor Necrosis Factor-α-converting Enzyme Mediates the Inducible Cleavage of Fractalkine*
It is reported that tumor necrosis factor-α-converting enzyme (TACE) is primarily responsible for the inducible cleavage of FK, and a potentially important link between local generation of potent cytokines and control of the balance between the cell adhesion and chemotactic properties of Fk is identified.


Regulation of tumour necrosis factor-α processing by a metalloproteinase inhibitor
The data suggest that TNF-α processing is mediated by a unique Zn2+ endopeptidase which is inhibited by GI 129471 and would represent a novel target for therapeutic intervention in TNF -α associated pathologies.
Processing of tumour necrosis factor-α precursor by metalloproteinases
It is shown that the release of mature TNF-α from leukocytes cultured in vitro is specifically prevented by synthetic hydroxamic acid-based metalloproteinase inhibitors, which also prevent the release into the circulation of endotoxin challenged rats.
Relaxed specificity of matrix metalloproteinases (MMPS) and TIMP insensitivity of tumor necrosis factor-alpha (TNF-alpha) production suggest the major TNF-alpha converting enzyme is not an MMP.
It is concluded that a non-matrix metalloproteinase is the major physiological tumor necrosis factor-alpha convertase.
Matrix metalloproteinases and their inhibitors in connective tissue remodeling
  • J. Woessner
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1991
Latency is overcome by physical, chemical, and enzymatic treatments that separate the cysteine residue from the zinc Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP‐1 binding site.
Human vascular smooth muscle cells. Target for and source of tumor necrosis factor.
SMC both respond to both TNF and lymphotoxin and can produce TNF-alpha, a cytokine with numerous effects on vascular cells of potential significance in the pathophysiology of septic shock and other inflammatory conditions.
Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated cytotoxic macrophages.
Macrophage cytotoxicity against this cell but not against the TNF-resistant P815 mastocytoma, was completely inhibitable by a specific anti-TNF serum also in the absence of measurable secreted TNF.
Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing
A therapeutic agent which inhibited the release of tumour necrosis factor, but did not reduce the cell-associated activity or the level of lymphotoxin-α, might preserve the benefits of these cytokines while preventing tumour Necrosis factor-induced damage.
MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains
The mouse and human homologue of a widely expressed cellular disintegrin is cloned and sequenced, and it is proposed that MDC9 might function as a membrane-anchored integrin ligand or metalloprotease, or that it may combine both activities in one protein.
The tumor necrosis factor ligand and receptor families.
Tumor necrosis factor and lymphotoxin-α were isolated more than 10 years ago on the basis of their ability to kill tumor cells in vitro and to cause hemorrhagic necrosis of transplantable tumors in mice, and a factor known as cachectin was isolated from mouse macrophages, sequenced, and shown to be identical to TNF.