ArticleThe Journal of biological chemistry2002
The ordered and compartment-specfific autoproteolytic removal of the furin intramolecular chaperone is required for enzyme activation.
Article in The Journal of biological chemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 144 citations in OpenAlex.
- TMPRSS2-induced Golgi disruption restricts the incorporation of virus envelope glycoproteins into virions.EMBO reports · 2026Article
- Beyond assembly: functions of the coronavirus M protein.Virology journal · 2026Review
- Beyond Processing: Furin as a Central Hub in Viral Pathogenesis and Genetic Susceptibility.Biomolecules · 2025Review
- Intracellular trafficking of furin enhances cellular intoxication by recombinant immunotoxins based on Pseudomonas exotoxin A.Biology open · 2025Article
- Article
- Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif.Reviews in medical virology · 2025Review
- The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signalling.Cardiovascular research · 2024Article
- Development and Prospects of Furin Inhibitors for Therapeutic Applications.International journal of molecular sciences · 2024Review
- Development of a SARS-CoV-2 neutralization assay based on a pseudotyped virus using a HIV system.MedComm · 2024Article
- Exploring the novel SNPs in neuroticism and birth weight based on GWAS datasets.BMC medical genomics · 2023Article
- Activation of themBio · 2023Article
- GRP75 as a functional element of cholix transcytosis.Tissue barriers · 2023Article
- Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.International journal of molecular sciences · 2022Review
- Testicular Germ Cell Tumours and Proprotein Convertases.Cancers · 2022Review
- How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?Viruses · 2021Review
- A review on potential of natural products in the management of COVID-19.RSC advances · 2021Review
- Patterns and tempo of PCSK9 pseudogenizations suggest an ancient divergence in mammalian cholesterol homeostasis mechanisms.Genetica · 2021Article
- Identification of Novel Genetic Regulatory Region for Proprotein Convertase FURIN and Interferon Gamma in T Cells.Frontiers in immunology · 2021Article
- Article
- Critical Evaluation of Strategies for the Production of Blood Coagulation Factors in Plant-Based Systems.Frontiers in plant science · 2019Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The propeptide of furin has multiple roles in guiding the activation of the endoprotease in vivo. The 83-residue N-terminal propeptide is autoproteolytically excised in the endoplasmic reticulum (ER) at the consensus furin site, -Arg(104)-Thr-Lys-Arg(107)-, but remains bound to furin as a potent autoinhibitor. Furin lacking the propeptide is ER-retained and proteolytically inactive. Co-expression with the propeptide, however, restores trans-Golgi network (TGN) localization and enzyme activity, indicating that the furin propeptide is an intramolecular chaperone. Blocking this step results in localization to the ER-Golgi intermediate compartment (ERGIC)/cis-Golgi network (CGN), suggesting the ER and ERGIC/CGN recognize distinct furin folding intermediates. Following transport to the acidified TGN/endosomal compartments, furin cleaves the bound propeptide at a second, internal P1/P6 Arg site (-Arg-Gly-Val(72)-Thr-Lys-Arg(75)-) resulting in propeptide dissociation and enzyme activation. Cleavage at Arg(75), however, is not required for proper furin trafficking. Kinetic analyses of peptide substrates indicate that the sequential pH-modulated propeptide cleavages result from the differential recognition of these sites by furin. Altering this preference by converting the internal site to a canonical P1/P4 Arg motif (Val(72) --> Arg) caused ER retention and blocked activation of furin, demonstrating that the structure of the furin propeptide mediates folding of the enzyme and directs its pH-regulated, compartment-specific activation in vivo.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.