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

FEBS Letters

Smith, Bryan J³  Slocombe, Patrick M³  Webster, Ailsa³  Shelley, Chris³  Hutton, Mike¹  Amour, Augustin¹  Stephens, Paul E³  Docherty, Andrew J.P³  Murphy, Gillian¹  Butler, Michael¹  Knight, C.Graham²  Knäuper, Vera¹ 

[1] School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK;Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK;Celltech Therapeutics Ltd, 216 Bath Road, Slough SL1 4EN, UK

关键词: Metalloproteinase;    Disintegrin metalloproteinase;    Tissue inhibitor of metalloproteinases;    Tumour necrosis factor;    TNF-α converting enzyme;    DMSO;    dimethylsulfoxide;    Dnp;    2;    4-dinitrophenyl;    Fmoc;    9-fluorenylmethoxycarbonyl;    HATU;    N-[(dimethylamino)-1H-1;    2;    3-triazolo[4;    5b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide;    HOAt;    7-aza-1-hydroxybenzotriazole;    HPLC;    high performance liquid chromatography;    Mca;    (7-methoxycoumarin-4-yl)acetyl;    NS0;    Non-secretor zero;    PAL;    peptide amide linker;    PEG;    poly(ethylene glycol);    PS;    polystyrene;    PVDF;    polyvinylidene difluoride;    SDS-PAGE;    sodium dodecyl sulfate polyacrylamide gel electrophoresis;    TFA;    trifluoroacetic acid;   

DOI  :  10.1016/S0014-5793(98)01031-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown