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TNF‐α converting enzyme (TACE) is inhibited by TIMP‐3
Author(s) -
Amour Augustin,
Slocombe Patrick M,
Webster Ailsa,
Butler Michael,
Knight C.Graham,
Smith Bryan J,
Stephens Paul E,
Shelley Chris,
Hutton Mike,
Knäuper Vera,
Docherty Andrew J.P,
Murphy Gillian
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01031-x
Subject(s) - disintegrin , metalloproteinase , matrix metalloproteinase , enzyme , secretion , chemistry , cytokine , peptide , fusion protein , tumor necrosis factor alpha , inflammation , biochemistry , microbiology and biotechnology , biology , recombinant dna , immunology , gene
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.