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
  • 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.