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

Publisher: John Wiley & Sons Ltd Country of Publication: England NLM ID: 0155157 Publication Model: Print Cited Medium: Print ISSN: 0014-5793 (Print) Linking ISSN: 00145793 NLM ISO Abbreviation: FEBS Lett Subsets: MEDLINE

Publication: Jan. 2016- : West Sussex : John Wiley & Sons Ltd.
Original Publication: Amsterdam, North-Holland on behalf of the Federation of European Biochemical Societies.

Enzyme Precursors/*metabolism ; Metalloendopeptidases/*metabolism ; Proprotein Convertases/*metabolism ; Tumor Necrosis Factor-alpha/*metabolism; ADAM Proteins ; ADAM17 Protein ; Amino Acid Sequence ; Animals ; Cell Line, Tumor ; Cells, Cultured ; Enzyme Activation/drug effects ; Enzyme Activation/physiology ; Enzyme Precursors/chemistry ; Furin/antagonists & inhibitors ; Furin/deficiency ; Furin/genetics ; Furin/metabolism ; Gene Expression Regulation, Enzymologic/drug effects ; Gene Expression Regulation, Enzymologic/physiology ; Humans ; Jurkat Cells ; Metalloendopeptidases/chemistry ; Proprotein Convertases/antagonists & inhibitors ; Proprotein Convertases/genetics ; Protease Inhibitors/pharmacology ; Rats ; Receptors, Tumor Necrosis Factor/metabolism ; Recombinant Proteins/antagonists & inhibitors ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Synovial Membrane/cytology ; Transfection ; alpha 1-Antitrypsin/genetics ; alpha 1-Antitrypsin/pharmacology

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.

0 (Enzyme Precursors)
0 (Protease Inhibitors)
0 (Receptors, Tumor Necrosis Factor)
0 (Recombinant Proteins)
0 (Tumor Necrosis Factor-alpha)
0 (alpha 1-Antitrypsin)
EC 3.4.21.- (Proprotein Convertases)
EC 3.4.21.75 (Furin)
EC 3.4.24.- (ADAM Proteins)
EC 3.4.24.- (Metalloendopeptidases)
EC 3.4.24.86 (ADAM17 Protein)
EC 3.4.24.86 (ADAM17 protein, human)
EC 3.4.24.86 (Adam17 protein, rat)

Date Created: 20031119 Date Completed: 20031218 Latest Revision: 20190621

20231215

10.1016/s0014-5793(03)01159-1

14623079