ArticleNature communications2014
Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 71 citations in OpenAlex.
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- The EF-hand domain of MINDY3 is a ubiquitin and RAD23 UBL-binding domain.EMBO reports · 2026Article
- TgJosephin and TgRad23 are important for anti-IFN-γ virulence via deubiquitination of SPM1 inmSphere · 2026Article
- Rad23b exacerbates pathological aggregates through disrupting proteasome functions in Spinocerebellar ataxia type 3.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- Polyglutamine-Expanded Ataxin-3 Accelerates CFTR Degradation Through K63-Linked Ubiquitination to Exacerbate Microglial Inflammation.ASN neuro · 2026Article
- UBL7 is indispensable for spermiogenesis through protecting critical factors from excessive degradation by proteasomes.Nature communications · 2025Article
- Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease.Neurobiology of disease · 2025Article
- Proteostasis disruption and lipid dyshomeostasis in neurodegeneration: exploring common druggable targets across sporadic and monogenic disorders.Frontiers in molecular neuroscience · 2025Review
- The Role of Protein Quantity Control in Polyglutamine Spinocerebellar Ataxias.Cerebellum (London, England) · 2024Review
- ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.Expert reviews in molecular medicine · 2024Review
- Progressive degeneration in a new Drosophila model of spinocerebellar ataxia type 7.Scientific reports · 2024Article
- The deubiquitinase function of ataxin-3 and its role in the pathogenesis of Machado-Joseph disease and other diseases.The Biochemical journal · 2024Review
- Progressive degeneration in a newResearch square · 2023Article
- Lysine 117 on ataxin-3 modulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3.Journal of the neurological sciences · 2023Article
- Phenotypic defects from the expression of wild-type and pathogenic TATA-binding proteins in new Drosophila models of Spinocerebellar Ataxia Type 17.G3 (Bethesda, Md.) · 2023Article
- Implications of specific lysine residues within ataxin-3 for the molecular pathogenesis of Machado-Joseph disease.Frontiers in molecular neuroscience · 2023Article
- KPNB1 modulates the Machado-Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP.Cellular and molecular life sciences : CMLS · 2022Article
- Article
- Ubiquitin-binding site 1 of pathogenic ataxin-3 regulates its toxicity inFrontiers in neuroscience · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Polyglutamine repeat expansion in ataxin-3 causes neurodegeneration in the most common dominant ataxia, spinocerebellar ataxia type 3 (SCA3). Since reducing levels of disease proteins improves pathology in animals, we investigated how ataxin-3 is degraded. Here we show that, unlike most proteins, ataxin-3 turnover does not require its ubiquitination, but is regulated by ubiquitin-binding site 2 (UbS2) on its N terminus. Mutating UbS2 decreases ataxin-3 protein levels in cultured mammalian cells and in Drosophila melanogaster by increasing its proteasomal turnover. Ataxin-3 interacts with the proteasome-associated proteins Rad23A/B through UbS2. Knockdown of Rad23 in cultured cells and in Drosophila results in lower levels of ataxin-3 protein. Importantly, reducing Rad23 suppresses ataxin-3-dependent degeneration in flies. We present a mechanism for ubiquitination-independent degradation that is impeded by protein interactions with proteasome-associated factors. We conclude that UbS2 is a potential target through which to enhance ataxin-3 degradation for SCA3 therapy.
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