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

Nature. 1997 Feb 20;385(6618):733-6. doi: 10.1038/385733a0.

M L Moss ¹, 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, J D Becherer

Affiliations

Affiliation

1 Department of Molecular Biochemistry, Glaxo Wellcome Research and Development Inc., Research Triangle Park, North Carolina 27709, USA.

PMID: 9034191 DOI: 10.1038/385733a0

Abstract

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.

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