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TACE/ADAM‐17 maturation and activation of sheddase activity require proprotein convertase activity
Author(s) -
Srour Nadim,
Lebel Annie,
McMahon Stephanie,
Fournier Isabelle,
Fugère Martin,
Day Robert,
Dubois Claire M
Publication year - 2003
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(03)01159-1
Subject(s) - proprotein convertase , proprotein convertases , chemistry , microbiology and biotechnology , biochemistry , biology , cholesterol , ldl receptor , lipoprotein
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 α 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‐α from transmembrane pro‐TNF‐α. We therefore conclude that furin, in addition to other candidate PCs, is involved in TACE maturation and activation.