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

Abstract

Tumour necrosis factor alpha (TNF alpha) is a cytokine that contributes to a variety of inflammatory disease states(1). The protein exists as a membrane bound precursor(2,3) 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(4), an enzyme implicated in myelin degradation, and to KUZ(5), 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.

Authors: Moss, M.L., Jin, S.-L.C., Milla, M.E., Burkhart, W., Carter, H.L., Chen, W.-J., Clay, W.C., Didsbury, J.R., Hassler, D., Hoffman, C.R., Kost, T.A., Lambert, M.H., Leesnitzer, M.A., McCauley, P., McGeehan, G., Mitchell, J., Moyer, M., Pahel, G., Rocque, W.
Journal: Nature, 385: 733-736
Year: 1997
PubMed: Find in PubMed