Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha.

doi:10.1038/385733a0

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Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha.

M L Moss, S L Jin, M E Milla, D M Bickett, W Burkhart, H L Carter, W J Chen, W C Clay, J R Didsbury, D Hassler, C R Hoffman, T A Kost, M H Lambert, M A Leesnitzer, P McCauley, G McGeehan, J Mitchell, M Moyer, G Pahel, W Rocque, L K Overton, F Schoenen, T Seaton, J L Su and J D Becherer Nature 385(6618):733-6 (1997) PMID 9034191

Tumour-necrosis factor-alpha (TNF-alpha) is a cytokine that contributes to a variety of inflammatory disease states. The protein exists as a membrane-bound precursor of relative molecular mass 26K which can be processed by a TNF-alpha-converting enzyme (TACE), to generate secreted 17K mature TNF-alpha. We have purified TACE and cloned its complementary DNA. TACE is a membrane-bound disintegrin metalloproteinase. Structural comparisons with other disintegrin-containing enzymes indicate that TACE is unique, with noteable sequence identity to MADM, an enzyme implicated in myelin degradation, and to KUZ, a Drosophila homologue of MADM important for neuronal development. The expression of recombinant TACE (rTACE) results in the production of functional enzyme that correctly processes precursor TNF-alpha to the mature form. The rTACE provides a readily available source of enzyme to help in the search for new anti-inflammatory agents that target the final processing stage of TNF-alpha production.

DOI: 10.1038/385733a0
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