TNF‐α converting enzyme (TACE) is inhibited by TIMP‐3

Augustin Amour(University of East Anglia), Patrick M. Slocombe, Ailsa Webster, Michael J. Butler(University of East Anglia), Christopher G. Knight(University of Cambridge), Bryan John Smith, Paul E. Stephens, Chris Shelley, Mike Hutton(University of East Anglia), Vera Knäuper(University of East Anglia), Andrew Docherty, Gillian Murphy(University of East Anglia)
FEBS Letters
September 11, 1998
10.1016/s0014-5793(98)01031-x
Cited by 607

Abstract

TNF-alpha converting enzyme (TACE; ADAM-17) is a membrane-bound disintegrin metalloproteinase that processes the membrane-associated cytokine proTNF-alpha 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-alpha secretion is involved.

Related Papers

Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α
Marcia L. Moss, S.-L. Catherine Jin, Marcos E. Milla et al.|Nature|1997|1.6k
The Behavior and Significance of Slow‐Binding Enzyme Inhibitors
John F. Morrison, Christopher T. Walsh|Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects|1988|842
The metzincins — Topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a super family of zinc‐peptidases
Walter Stöcker, Frank Grams, Peter Reinemer et al.|Protein Science|1995|710
Membrane protein secretases
Nigel M. Hooper, Eric Karran, Anthony J. Turner|Biochemical Journal|1997|624
Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1
Franz-Xaver Gomis-R ̈th, K. Maskos, Michael Betz et al.|Nature|1997|619