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FEBS Lett. 2003 Nov 20;554(3):275-83.

TACE/ADAM-17 maturation and activation of sheddase activity require proprotein convertase activity.

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  • 1Immunology Division, Department of Pediatrics, Faculty of Medicine, UniversitĂ© de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.


Proprotein convertases (PCs) have been proposed to play a role in tumor necrosis factor-alpha converting enzyme (TACE) processing/activation. Using the furin-deficient LoVo cells, as well as the furin-proficient synoviocytes and HT1080 cells expressing the furin inhibitor alpha(1)-PDX, we demonstrate that furin activity alone is not sufficient for effective maturation and activation of the TACE enzyme. Data from in vitro and in vivo cleavage assays indicate that PACE-4, PC5/PC6, PC1 and PC2 can directly cleave the TACE protein and/or peptide. PC inhibition in macrophages reduced the release of soluble TNF-alpha from transmembrane pro-TNF-alpha. We therefore conclude that furin, in addition to other candidate PCs, is involved in TACE maturation and activation.

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