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

作者：Augustin Amour, Patrick M. Slocombe, Ailsa Webster, Michael J. Butler, Christopher G. Knight, Bryan John Smith, Paul E. Stephens, Chris Shelley, Mike Hutton, Vera Knäuper, Andrew Docherty, Gillian Murphy · 发表于：FEBS Letters · 年份：1998 · DOI：10.1016/s0014-5793(98)01031-x · 被引用次数：610 · 研究领域：Cell Adhesion Molecules Research、Protease and Inhibitor Mechanisms、HER2/EGFR in Cancer Research

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.