The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Abstract
Autosomal recessive juvenile parkinsonism (AR-JP), one of the most common familial forms of Parkinson disease, is characterized by selective dopaminergic neural cell death and the absence of the Lewy body, a cytoplasmic inclusion body consisting of aggregates of abnormally accumulated proteins. We previously cloned PARK2, mutations of which cause AR-JP (ref. 2), but the function of the gene product, parkin, remains unknown. We report here that parkin is involved in protein degradation as a ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7, and that mutant parkins from AR-JP patients show loss of the ubiquitin-protein ligase activity. Our findings indicate that accumulation of proteins that have yet to be identified causes a selective neural cell death without formation of Lewy bodies. Our findings should enhance the exploration of the molecular mechanisms of neurodegeneration in Parkinson disease as well as in other neurodegenerative diseases that are characterized by involvement of abnormal protein ubiquitination, including Alzheimer disease, other tauopathies, CAG triplet repeat disorders and amyotrophic lateral sclerosis.
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In the citing paper
“Parkin, the product of PARK2, is known to be a RINGfinger-containing E3-Ub ligase”
From Limb-Girdle Muscular Dystrophy Type 2H Associated with Mutation in TRIM32, a Putative E3-Ubiquitin–Ligase Gene (2002) · cites this paper as Shimura et al. 2000
In the citing paper
“Mutations in the Park2 gene, encoding the E3 ubiquitin-ligase parkin, are responsible for a familial form of Parkinson's disease (PD).”
From USP8 regulates mitophagy by removing K6‐linked ubiquitin conjugates from parkin (2014) · cites this paper as Shimura et al, 2000
In the citing paper
“Failure of the ubiquitin-proteasome system is implicated in the pathogenesis of both sporadic and familial PD [22,23,24,94,95,96].”
From Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson’s Disease and Dopa-Responsive Dystonia (2020) · cites this paper as [24]
Citations
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Cited by
Sorted by citations
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469
“…ubiquitinthe view that the cellular membrane is a key site of -synuclein action (Pronin et al., 2000; Ahn et al., 2002). ligase (Zhang et al., 2000; Shimura et al., 2000), a component of the ubiquitin-proteasome system that identifiesOne membrane-related function of -synuclein may be trafficking…”
BackgroundThe Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
Glickman, M. H., & Ciechanover, A. J. (2002) · Physiological Reviews · doi:10.1152/physrev.00027.2001 · Cited by 4,296
“Certain members, Mdm2 (42, 120, 280), Ubr1/ E3 (250, 367), and Parkin (411), for example, are monomers or homodimers and contain both the RING finger domain and the substrate-binding/recognition site in the same molecule.”
BackgroundMechanisms Underlying Ubiquitination
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PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
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Roles of CHOP/GADD153 in endoplasmic reticulum stress
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“stress, and overexpression of parkin confers resistance to both ER stress and mutant a-synuclein-induced toxicity.(104,105)”
Background
Metadata
- Authors
- Shimura, H., Hattori, N., Kubo, S.-I., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., & Suzuki, T.
- Affiliations
- Juntendo University (JP)
- Keio University (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Tanaka, Keiji
- ORCID
- Venue
- Nature Genetics
- Published
- 2000-07
- Volume
- 25
- Issue
- 3
- Pages
- 302-305
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1550876205
- Cited by
- 2,024
- References
- 30
- Citations by year
- 2026: 34 · 2025: 29 · 2024: 49 · 2023: 48 · 2022: 41 · 2021: 54 · 2020: 60 · 2019: 51 · 2018: 57 · 2017: 67 · 2016: 75 · 2015: 72 · 2014: 83 · 2013: 102 · 2012: 98
- FWCI
- 70.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- Parkin, PARK2, autosomal recessive juvenile parkinsonism, Parkinson's disease, ubiquitin-protein ligase, UbcH7, protein degradation, dopaminergic neuron death, Lewy bodies, neurodegeneration, ubiquitination, Alzheimer's disease, tauopathy, amyotrophic lateral sclerosis
- MeSH terms
- Humans, Ligases, Parkinson Disease, Recombinant Fusion Proteins, Tumor Cells, Cultured, Ubiquitins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
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