ArticleNature communications2018
The ubiquitin ligase UBR5 suppresses proteostasis collapse in pluripotent stem cells from Huntington's disease patients.
Article in Nature communications, 2018. 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 69 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases.Molecular neurobiology · 2023Pooled it
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- USP28 Deficiency is Linked to Impaired Ubiquitin-dependent Proteostasis in Huntington's Disease.Molecular neurobiology · 2026Article
- Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease.EMBO molecular medicine · 2026Article
- Causal Links Between the Plasma Lipidome and Cognitive Performance: Targets, Pathways, and Lifestyle Influences.Molecular neurobiology · 2026Article
- Insights into neurodevelopmental features of Huntington's disease from stem cell-derived models including organoids.Journal of Huntington's disease · 2026Review
- E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- Review
- Ubiquitination in the Nervous System: From Molecular Mechanisms to Disease Implications.Molecular neurobiology · 2025Review
- C9orf72 ALS-causing mutations lead to mislocalization and aggregation of nucleoporin Nup107 into stress granules.FEBS letters · 2025Article
- The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation.Nature aging · 2025Article
- Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5.Nature communications · 2025Article
- O-GlcNAc-modified HOXA9 suppresses ferroptosis via promoting UBR5-mediated SIRT6 degradation in nasopharyngeal carcinoma.Neoplasia (New York, N.Y.) · 2025Article
- Unraveling Molecular Targets for Neurodegenerative Diseases ThroughInternational journal of molecular sciences · 2025Review
- Ubiquitin-Proteasome-Mediated Protein Degradation and Disorders of the Central Nervous System.International journal of molecular sciences · 2025Review
- UBR-5 and UBE2D mediate timely exit from stem fate via destabilization of poly(A)-binding protein PABP-2 in cell state transition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington's disease.Nature cell biology · 2024Article
- Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- A short peptide protects from age-onset proteotoxicity.Aging cell · 2023Article
- Neuroprotective effects of hepatoma-derived growth factor in models of Huntington's disease.Life science alliance · 2023Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Induced pluripotent stem cells (iPSCs) undergo unlimited self-renewal while maintaining their potential to differentiate into post-mitotic cells with an intact proteome. As such, iPSCs suppress the aggregation of polyQ-expanded huntingtin (HTT), the mutant protein underlying Huntington's disease (HD). Here we show that proteasome activity determines HTT levels, preventing polyQ-expanded aggregation in iPSCs from HD patients (HD-iPSCs). iPSCs exhibit high levels of UBR5, a ubiquitin ligase required for proteasomal degradation of both normal and mutant HTT. Conversely, loss of UBR5 increases HTT levels and triggers polyQ-expanded aggregation in HD-iPSCs. Moreover, UBR5 knockdown hastens polyQ-expanded aggregation and neurotoxicity in invertebrate models. Notably, UBR5 overexpression induces polyubiquitination and degradation of mutant HTT, reducing polyQ-expanded aggregates in HD-cell models. Besides HTT levels, intrinsic enhanced UBR5 expression determines global proteostasis of iPSCs preventing the aggregation of misfolded proteins ensued from normal metabolism. Thus, our findings indicate UBR5 as a modulator of super-vigilant proteostasis of iPSCs.
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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.