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

FEBS Letters

Fournier, Isabelle²  McMahon, Stephanie¹  Lebel, Annie¹  Dubois, Claire M¹  Day, Robert³  Fugère, Martin³  Srour, Nadim¹ 

[1] Immunology Division, Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4;Laboratoire de Neuroimmunologie des Annélides, UMR CNRS 8017, Université des Sciences et Technologie de Lille, Lille, France;Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4

关键词: Tumor necrosis factor-α converting enzyme;    Tumor necrosis factor-α;    Proprotein convertase;    Furin;    LoVo cell;    AT-PDX;   

DOI  :  10.1016/S0014-5793(03)01159-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Proprotein convertases (PCs) have been proposed to play a role in tumor necrosis factor-α 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 α₁-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-α from transmembrane pro-TNF-α. We therefore conclude that furin, in addition to other candidate PCs, is involved in TACE maturation and activation.

【 授权许可】

Unknown