ArticleThe Journal of biological chemistry2013
Parkin ubiquitinates Tar-DNA binding protein-43 (TDP-43) and promotes its cytosolic accumulation via interaction with histone deacetylase 6 (HDAC6).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
- Nilotinib in Parkinson's disease: A systematic review and meta-analysis.Frontiers in aging neuroscience · 2022Pooled it
- LncRNAs LCETRL3 and LCETRL4 at chromosome 4q12 diminish EGFR-TKIs efficiency in NSCLC through stabilizing TDP43 and EIF2S1.Signal transduction and targeted therapy · 2022Trial
- Long-Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Trial
- Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial.JAMA neurology · 2020Trial
- Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease.Pharmacology research & perspectives · 2019Trial
- Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies.Journal of Parkinson's disease · 2016Trial
- The role of E3 ubiquitin ligases in selective types of macroautophagy.EMBO reports · 2026Review
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Rsp5/NEDD4 and ESCRT regulate TDP-43 toxicity and turnover via an endolysosomal clearance mechanism.The Journal of cell biology · 2026Article
- Review
- Ubiquitin signatures on aggregating proteins in neurodegeneration.Essays in biochemistry · 2025Review
- Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.Cells · 2025Review
- TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.Cell reports · 2025Article
- Ubiquitin-Proteasome-Mediated Protein Degradation and Disorders of the Central Nervous System.International journal of molecular sciences · 2025Review
- Pathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Biomolecular condensates and disease pathogenesis.Science China. Life sciences · 2024Review
- Post-Translational Variants of Major Proteins in Amyotrophic Lateral Sclerosis Provide New Insights into the Pathophysiology of the Disease.International journal of molecular sciences · 2024Review
- Frontotemporal-TDP and LATE Neurocognitive Disorders: A Pathophysiological and Genetic Approach.Brain sciences · 2023Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The importance of E3 ubiquitin ligases, involved in the degradation of misfolded proteins or promotion of protein-protein interaction, is increasingly recognized in neurodegeneration. TDP-43 is a predominantly nuclear protein, which regulates the transcription of thousands of genes and binds to mRNA of the E3 ubiquitin ligase Parkin to regulate its expression. Wild type and mutated TDP-43 are detected in ubiquitinated forms within the cytosol in several neurodegenerative diseases. We elucidated the mechanisms of TDP-43 interaction with Parkin using transgenic A315T mutant TDP-43 (TDP43-Tg) mice, lentiviral wild type TDP-43, and Parkin gene transfer rat models. TDP-43 expression increased Parkin mRNA and protein levels. Lentiviral TDP-43 increased the levels of nuclear and cytosolic protein, whereas Parkin co-expression mediated Lys-48 and Lys-63-linked ubiquitin to TDP-43 and led to cytosolic co-localization of Parkin with ubiquitinated TDP-43. Parkin and TDP-43 formed a multiprotein complex with HDAC6, perhaps to mediate TDP-43 translocation. In conclusion, Parkin ubiquitinates TDP-43 and facilitates its cytosolic accumulation through a multiprotein complex with HDAC6.
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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.