TNF‐α converting enzyme (TACE) is inhibited by TIMP‐3
Open Access
- 11 September 1998
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 435 (1) , 39-44
- https://doi.org/10.1016/s0014-5793(98)01031-x
Abstract
TNF‐α converting enzyme (TACE; ADAM‐17) is a membrane‐bound disintegrin metalloproteinase that processes the membrane‐associated cytokine proTNF‐α to a soluble form. Because of its putative involvement in inflammatory diseases, TACE represents a significant target for the design of specific synthetic inhibitors as therapeutic agents. In order to study its inhibition by tissue inhibitors of metalloproteinases (TIMPs) and synthetic inhibitors of metalloproteinases, the catalytic domain of mouse TACE (rTACE) was overexpressed as a soluble Ig fusion protein from NS0 cells. rTACE was found to be well inhibited by peptide hydroxamate inhibitors as well as by TIMP‐3 but not by TIMP‐1, ‐2 and ‐4. These results suggest that TIMP‐3, unlike the other TIMPs, may be important in the modulation of pathological events in which TNF‐α secretion is involved.Keywords
This publication has 36 references indexed in Scilit:
- Partial purification and characterization of a tumor necrosis factor-α converting activityEuropean Journal of Immunology, 1997
- A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cellsNature, 1997
- Purification of ADAM 10 from bovine spleen as a TNFα convertaseFEBS Letters, 1997
- Relaxed Specificity of Matrix Metalloproteinases (MMPS) and TIMP Insensitivity of Tumor Necrosis Factor-α (TNF-α) Production Suggest the Major TNF-α Converting Enzyme Is Not an MMPBiochemical and Biophysical Research Communications, 1996
- The metzincins — Topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a super family of zinc‐peptidasesProtein Science, 1995
- Antibodies that activate β2 integrins can generate different ligand binding statesEuropean Journal of Immunology, 1995
- Site-directed mutations that alter the inhibitory activity of the tissue inhibitor of metalloproteinases-1: importance of the N-terminal region between cysteine 3 and cysteine 13Biochemistry, 1992
- A novel coumarin‐labelled peptide for sensitive continuous assays of the matrix metalloproteinasesFEBS Letters, 1992
- Cachectin/tumor necrosis factor exerts endocrine, paracrine, and autocrine control of inflammatory responses.The Journal of cell biology, 1988
- The Behavior and Significance of Slow‐Binding Enzyme InhibitorsPublished by Wiley ,1988