ArticleThe Journal of biological chemistry2011
The proprotein convertase PC7: unique zymogen activation and trafficking pathways.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Stress-induced secretory pathway disruption causes atypical metalloproteinase transport in PMM2-CDG.iScience · 2026Article
- Golgi-associated TRAF6 as a regulator of protein convertase FURIN for insulin receptor precursor processing.Science China. Life sciences · 2025Article
- Structural insights into proprotein convertase activation facilitate the engineering of highly specific furin inhibitors.Nature communications · 2025Article
- Blockade of colon cancer metastasis via single and double silencing ofJournal for immunotherapy of cancer · 2025Article
- The Biology and Clinical Implications of PCSK7.Endocrine reviews · 2025Review
- Targeting proprotein convertase subtilisin/kexin type 7 in macrophages as a therapeutic strategy to mitigate myocardial infarction-induced inflammation.BMB reports · 2024Article
- Oligonucleotide therapies for nonalcoholic steatohepatitis.Molecular therapy. Nucleic acids · 2024Review
- Circulating PCSK7 Level is Independently Associated with Obesity, Triglycerides Level and Fatty Liver Index in a General Population without Medication.Journal of atherosclerosis and thrombosis · 2022Article
- Post-Transcriptional Effects of miRNAs on PCSK7 Expression and Function: miR-125a-5p, miR-143-3p, and miR-409-3p as Negative Regulators.Metabolites · 2022Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- The motif EThe Journal of biological chemistry · 2020Article
- Article
- Anthrax toxin requires ZDHHC5-mediated palmitoylation of its surface-processing host enzymes.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Extracellular Processing of Lysyl Oxidase-like 2 and Its Effect on Amine Oxidase Activity.Biochemistry · 2018Article
- Enhanced Proteolytic Processing of Recombinant Human Coagulation Factor VIII B-Domain Variants by Recombinant Furins.Molecular biotechnology · 2016Article
- Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder.Molecular and cellular biology · 2015Article
- PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation.The Journal of cell biology · 2015Article
- The Golgi apparatus regulates cGMP-dependent protein kinase I compartmentation and proteolysis.American journal of physiology. Cell physiology · 2015Article
- The Processed Amino-Terminal Fragment of Human TLR7 Acts as a Chaperone To Direct Human TLR7 into Endosomes.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Is there a link between proprotein convertase PC7 activity and human lipid homeostasis?FEBS open bio · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The zymogen activation mechanism and physiological functions of the most ancient and highly conserved basic amino acid-specific proprotein convertase 7 (PC7) are not known. Herein, we characterized the biosynthesis, subcellular localization, and trafficking of the membrane-bound full-length rat and human PC7. The prosegment of PC7 is primarily secreted alone as a non-inhibitory protein via the conventional, Golgi-dependent, secretory pathway. Mature PC7 is partially sulfated and thus reaches the cell surface via the conventional route. However, a fraction of PC7 reaches the cell surface through a brefeldin A- and COPII-independent unconventional secretory pathway. The latter trafficking may explain the rapid (<10 min) transit of a fraction of PC7 from the ER to the cell surface. Electron microscopy further confirmed the localization of PC7 to the cell surface of HEK293 cells. Within the cytosolic tail, only two cysteines (Cys(699) and Cys(704)) are palmitoylated, but this modification does not affect the choice of trafficking pathway. Swapping the transmembrane-cytosolic tail (TMCT) sequences of the convertases Furin and PC7 revealed that PC7(TMCT-Furin) is much more sulfated and hence traffics more efficiently through the conventional secretory pathway. In contrast, the Furin(TMCT-PC7) is no longer sulfated and thus reaches the cell surface by the unconventional pathway. Because trafficking of PC7(CT-Furin) and Furin(CT-PC7) resemble their wild type counterparts, we deduce that the transmembrane domain of PC7 regulates the sorting of PC7 toward the unconventional secretory pathway. In conclusion, PC7 is distinct from other proprotein convertases in its zymogen activation, subcellular localization, and trafficking.
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