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Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Shimura H, Hattori N, Kubo Si, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K et al.. Nature genetics, 2000-07-01
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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.
Why it matters
This laboratory study found that parkin — the protein made by the gene mutated in an inherited juvenile form of Parkinson's disease — helps tag proteins for disposal as a ubiquitin-protein ligase working with the enzyme UbcH7, and that faulty parkin from patients has lost this activity. The authors conclude that a build-up of proteins "that have yet to be identified" kills dopamine-producing nerve cells without forming Lewy bodies. They suggest the finding may help research into Alzheimer's and other diseases involving abnormal protein tagging, but the study tested nothing in Alzheimer's disease and no treatment.
Study details
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature genetics) |
| Journal's citation record | 4 / 4 | Nature Genetics: journal h-index 776 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2000 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 2,028 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 72.4 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 6 / 6 | Cited 69.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 110 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Toshiaki Suzuki: h-index 28 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Kyoto University: institution h-index 1,156 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10888878) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Shimura, H., Hattori, N., Si, K., Mizuno, Y., Asakawa, S., Minoshima, S., et al. (2000). Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nature genetics. https://doi.org/10.1038/77060
Vancouver
Shimura H, Hattori N, Si K, Mizuno Y, Asakawa S, Minoshima S, et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nature genetics. 2000. doi:10.1038/77060. PMID: 10888878.
BibTeX
@article{shimura2000-10888878,
author = {Shimura, H. and Hattori, N. and Si, Kubo and Mizuno, Y. and Asakawa, S. and Minoshima, S. and Shimizu, N. and Iwai, K. and others},
title = {{Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase}},
journal = {Nature genetics},
year = {2000},
doi = {10.1038/77060},
pmid = {10888878},
url = {https://doi.org/10.1038/77060}
}
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