ArticleCellular and molecular life sciences : CMLS2015
Parkin-mediated K63-polyubiquitination targets ubiquitin C-terminal hydrolase L1 for degradation by the autophagy-lysosome system.
Article in Cellular and molecular life sciences : CMLS, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases.Molecular neurobiology · 2023Pooled it
- The Emerging Role of UCHL1 in Neurological and Musculoskeletal Diseases.Immunology and cell biology · 2026Review
- UBE2C at the crossroads of cell cycle regulation and DNA damage response in cancer.Cell biology and toxicology · 2026Review
- Modulation of the tumor microenvironment by the ubiquitin-proteasome system in colorectal cancer.Journal of translational medicine · 2025Review
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- Computational association in parkinson's disease SNPs with brain structural and functional alterations.Neurogenetics · 2025Article
- Inhibition of UBE2C Promotes Parkin-Mediated K63-Linked Ubiquitination of TOP2A to Induce Senescence and Increase Sensitivity of Doxorubicin in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025Review
- SFXN2 contributes mitochondrial dysfunction-induced apoptosis as a substrate of Parkin.Frontiers in cellular neuroscience · 2025Article
- Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Ubiquitin Carboxyl-Terminal Hydrolase L1 and Its Role in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy.Genes & diseases · 2023Review
- Pathological mechanisms of neuroimmune response and multitarget disease-modifying therapies of mesenchymal stem cells in Parkinson's disease.Stem cell research & therapy · 2023Review
- Atypical Ubiquitination and Parkinson's Disease.International journal of molecular sciences · 2022Review
- Ubiquitin-proteasome system (UPS) as a target for anticancer treatment.Archives of pharmacal research · 2020Review
- A new target for an old DUB: UCH-L1 regulates mitofusin-2 levels, altering mitochondrial morphology, function and calcium uptake.Redox biology · 2020Article
- Coupling Conjugation and Deconjugation Activities to Achieve Cellular Ubiquitin Dynamics.Trends in biochemical sciences · 2020Review
- Ubiquitin Carboxyl-Terminal Hydrolases and Human Malignancies: The Novel Prognostic and Therapeutic Implications for Head and Neck Cancer.Frontiers in oncology · 2020Review
- Targeted Multiple Reaction Monitoring Analysis of CSF Identifies UCHL1 and GPNMB as Candidate Biomarkers for ALS.Journal of molecular neuroscience : MN · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a key neuronal deubiquitinating enzyme which is mutated in Parkinson disease (PD) and in childhood-onset neurodegenerative disorder with optic atrophy. Furthermore, reduced UCH-L1 protein levels are associated with a number of neurodegenerative diseases, whereas up-regulation of UCH-L1 protein expression is found in multiple types of cancer. However, very little is known about how UCH-L1 protein level is regulated in cells. Here, we report that UCH-L1 is a novel interactor and substrate of PD-linked E3 ubiquitin-protein ligase parkin. We find that parkin mediates K63-linked polyubiquitination of UCH-L1 in cooperation with the Ubc13/Uev1a E2 ubiquitin-conjugating enzyme complex and promotes UCH-L1 degradation by the autophagy-lysosome pathway. Targeted disruption of parkin gene expression in mice causes a significant decrease in UCH-L1 ubiquitination with a concomitant increase in UCH-L1 protein level in brain, supporting an in vivo role of parkin in regulating UCH-L1 ubiquitination and degradation. Our findings reveal a direct link between parkin-mediated ubiquitin signaling and UCH-L1 regulation, and they have important implications for understanding the roles of these two proteins in health and disease.
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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.