ArticleThe Journal of biological chemistry2014
A new paradigm for enzymatic control of α-cleavage and β-cleavage of the prion protein.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 101 citations in OpenAlex.
- Cellular prion protein and its derived peptides: multifaceted roles in neurodegenerative diseases and potential as biomarkers.Cell & bioscience · 2026Review
- Copper Coordination to the Prion Fragment (95-126): Implications for Neurodegenerative Diseases.International journal of molecular sciences · 2026Article
- Bovine Spongiform Encephalopathy: An Integrated Review of Prion Mechanisms, Neuroanatomy, and Control.Veterinary sciences · 2026Review
- Recent Development on Copper-Sensor and its Biological Applications: A Review.Journal of fluorescence · 2025Review
- A Julolidine Coupled Azine-based Reversible Chromo-fluorogenic Probe for Specific Detection of CuJournal of fluorescence · 2025Article
- Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.Journal of neurochemistry · 2025Review
- Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.Acta neuropathologica · 2024Article
- A novel carbazole-based fluorometric and colorimetric sensor for the highly sensitive and specific detection of CuRSC advances · 2023Article
- Redox mechanisms and their pathological role in prion diseases: The road to ruin.PLoS pathogens · 2023Review
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Prion Protein: The Molecule of Many Forms and Faces.International journal of molecular sciences · 2022Review
- Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance.Molecules (Basel, Switzerland) · 2022Review
- Endoproteolysis of cellular prion protein by plasmin hinders propagation of prions.Frontiers in molecular neuroscience · 2022Article
- A Soluble PrPJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Article
- β-Cleavage of the prion protein in the human eye: Implications for the spread of infectious prions and human ocular disorders.Experimental eye research · 2021Article
- Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part II: strategies for therapeutics development.Expert review of neurotherapeutics · 2021Article
- Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part I. a literature review.Expert review of neurotherapeutics · 2021Review
- A soluble derivative of PrPThe Journal of biological chemistry · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The cellular form of the prion protein (PrP(C)) is found in both full-length and several different cleaved forms in vivo. Although the precise functions of the PrP(C) proteolytic products are not known, cleavage between the unstructured N-terminal domain and the structured C-terminal domain at Lys-109↓His-110 (mouse sequence), termed α-cleavage, has been shown to produce the anti-apoptotic N1 and the scrapie-resistant C1 peptide fragments. β-Cleavage, residing adjacent to the octarepeat domain and N-terminal to the α-cleavage site, is thought to arise from the action of reactive oxygen species produced from redox cycling of coordinated copper. We sought to elucidate the role of key members of the ADAM (a disintegrin and metalloproteinase) enzyme family, as well as Cu(2+) redox cycling, in recombinant mouse PrP (MoPrP) cleavage through LC/MS analysis. Our findings show that although Cu(2+) redox-generated reactive oxygen species do produce fragmentation corresponding to β-cleavage, ADAM8 also cleaves MoPrP in the octarepeat domain in a Cu(2+)- and Zn(2+)-dependent manner. Additional cleavage by ADAM8 was observed at the previously proposed location of α-cleavage, Lys-109↓His-110 (MoPrP sequencing); however, upon addition of Cu(2+), the location of α-cleavage shifted by several amino acids toward the C terminus. ADAM10 and ADAM17 have also been implicated in α-cleavage at Lys-109↓His-110; however, we observed that they instead cleaved MoPrP at a novel location, Ala-119↓Val-120, with additional cleavage by ADAM10 at Gly-227↓Arg-228 near the C terminus. Together, our results show that MoPrP cleavage is far more complex than previously thought and suggest a mechanism by which PrP(C) fragmentation responds to Cu(2+) and Zn(2+).
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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.