TACE/ADAM‐17 maturation and activation of sheddase activity require proprotein convertase activity
Open accessAbstract
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.
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Adam17 and Arg2 proteins affect Hif-1α stability and activity by regulating production of tumor necrosis factor α (TNF-α) and nitric oxide, respectively, whereas Mmp3 has key roles in numerous physiological processes.
“The Adam17 and Arg2 proteins affect Hif-1α stability and activity by regulating production of tumor necrosis factor α (TNF-α) 31,32 and nitric oxide, respectively 33,34 , whereas Mmp3 has key roles in numerous physiological processes 35 .”
From The yak genome and adaptation to life at high altitude (2012) · cites this paper as [31]
The Introduction (page not available) identifies ADAM17/TACE as an enzyme that cleaves TNF-α into a soluble form. Section 3.5 reports that inhibiting TACE processing reduces TNF-α release. The paper does not establish the attributed effect on HIF-1α stability or activity; the Arg2 and Mmp3 clauses carry separate citations. (LLM, conf=0.84)
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The yak genome and adaptation to life at high altitude
Qiu, Q., Zhang, G., Ma, T., Qian, W., Wang, J., Ye, Z., Cao, C., Hu, Q., Kim, J., Larkin, D. M., et al. (2012) · Nature Genetics · doi:10.1038/ng.2343 · Cited by 971 · see citing works
- Authors
- Srour, N., Lebel, A., McMahon, S., Fournier, I., Fugère, M., Day, R., & Dubois, C. M.
- Affiliations
- Université de Sherbrooke (CA)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Dubois, Claire M
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2003-10-17
- Volume
- 554
- Issue
- 3
- Pages
- 275-283
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2077474356
- Cited by
- 103
- References
- 55
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Keywords
- ADAM17, proprotein convertases, furin, enzyme maturation, enzyme activation, PC1, PC2, soluble TNF-alpha, macrophages
- MeSH terms
- ADAM17 Protein, alpha 1-Antitrypsin, Amino Acid Sequence, Animals, Cells, Cultured, Enzyme Activation, Enzyme Precursors, Humans, Metalloendopeptidases, Protease Inhibitors, Recombinant Proteins, Synovial Membrane, Transfection, Tumor Necrosis Factor-alpha, Gene Expression Regulation, Enzymologic, Receptors, Tumor Necrosis Factor, Jurkat Cells, Proprotein Convertases, Furin, Cell Line, Tumor, Rats, ADAM Proteins
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