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

Marcia L. Moss, S.-L. Catherine Jin, Marcos E. Milla, William Burkhart, H. Luke Carter, Wen-Ji Chen, William C. Clay, John R. Didsbury, Daniel Hassler, Christine R. Hoffman, Thomas A. Kost, Millard H. Lambert, M. Anthony Leesnitzer, Philip McCauley, Gerard McGeehan, Justin Mitchell, Mary Moyer, Gregory Pahel, Warren Rocque, Laurie K. Overton, Frank Schoenen, Theresa Seaton, Jui-Lan Su, Janet Warner, Derril Willard and J. David Becherer
Additional contact information
Marcia L. Moss: Glaxo Wellcome Research and Development Inc.
S.-L. Catherine Jin: Stanford University School of Medicine
Marcos E. Milla: Dow Corning Corporation
William Burkhart: Glaxo Wellcome Research and Development Inc.
H. Luke Carter: Glaxo Wellcome Research and Development Inc.
Wen-Ji Chen: Glaxo Wellcome Research and Development Inc.
William C. Clay: Glaxo Wellcome Research and Development Inc.
John R. Didsbury: Glaxo Wellcome Research and Development Inc.
Daniel Hassler: Glaxo Wellcome Research and Development Inc.
Christine R. Hoffman: Glaxo Wellcome Research and Development Inc.
Thomas A. Kost: Glaxo Wellcome Research and Development Inc.
Millard H. Lambert: Glaxo Wellcome Research and Development Inc.
M. Anthony Leesnitzer: Glaxo Wellcome Research and Development Inc.
Philip McCauley: Glaxo Wellcome Research and Development Inc.
Gerard McGeehan: RPR
Justin Mitchell: Glaxo Wellcome Research and Development Inc.
Mary Moyer: Glaxo Wellcome Research and Development Inc.
Gregory Pahel: Glaxo Wellcome Research and Development Inc.
Warren Rocque: Glaxo Wellcome Research and Development Inc.
Laurie K. Overton: Glaxo Wellcome Research and Development Inc.
Frank Schoenen: Glaxo Wellcome Research and Development Inc.
Theresa Seaton: Dow Corning Corporation
Jui-Lan Su: Glaxo Wellcome Research and Development Inc.
Janet Warner: Glaxo Wellcome Research and Development Inc.
Derril Willard: Glaxo Wellcome Research and Development Inc.
J. David Becherer: Glaxo Wellcome Research and Development Inc.

Nature, 1997, vol. 385, issue 6618, 733-736

Abstract: Abstract Tumour-necrosis factor-α (TNF-α) is a cytokine that contributes to a variety of inflammatory disease states1. The protein exists as a membrane-bound precursor2,3 of relative molecular mass 26K which can be processed by a TNF-α-converting enzyme (TACE), to generate secreted 17K mature TNF-α. 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 MADM4, an enzyme implicated in myelin degradation, and to KUZ5, 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-α 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-α production.

Date: 1997
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DOI: 10.1038/385733a0

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